Objective  To assess the research landscape, focal themes, and evolving trends in traditional Chinese medicine (TCM) for treating liver cancer over the past two decades using bibliometric analysis, and to provide a reference for future research in this field.

Methods  Literature related to TCM treatment for liver cancer published between March 31, 2006, and March 31, 2025, was retrieved from the CNKI, WanFang, VIP, and Web of Science (WOS) Core Collection databases. Microsoft Excel 2021, CiteSpace and VOSviewer were used to visualize publication volumes, author and institutional distribution, and keyword co-occurrence networks.

Results  A total of 2,057 Chinese literature and 705 English literature were included. China contributed the highest number of literature (579 papers), while Saudi Arabia ranked first in terms of the centrality of its literature. The most prolific author was ZHAO Zenghu (13 papers), Guangzhou University of Chinese Medicine (147 papers) and Shanghai University of Traditional Chinese Medicine (44 papers) were the most productive institutions. Research hotspots had shifted from efficacy evaluation of traditional compound preparations to network pharmacology and molecular docking. The most frequently studied TCM components included cinobufagin, matrine, quercetin, and flavonoids.

Conclusion  Recent research paradigms in TCM for liver cancer are transitioning from conventional sin-gle-component analysis toward multi-omics integrated systems biology approaches. Advances in novel formulation development are addressing the limitations of traditional administration routes, and TCM is expected to upgrade from adjuvant therapy to a comprehensive treatment regimen for liver cancer, which will promote the development of traditional medicine and modern oncology.

1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6): 394-424. DOI: 10.3322/caac.21492.

2. Li Z, Duan D, Li L, et al. Tumor-associated macrophages in anti-PD-1/PD-L1 immunotherapy for hepatocellular carcinoma: recent research progress[J]. Front Pharmacol, 2024, 15: 1382256. DOI: 10.3389/fphar.2024.1382256.

3. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. DOI: 10.3322/caac.21660.

4. 曹广文. 我国原发性肝癌的流行病学特征及精准防控[J]. 广西医科大学学报, 2024, 41(11): 1455-1463. [Cao GW. Epidemiological characteristics and precise prophylaxis and control of primary liver cancer in China[J]. Journal of Guangxi Medical University, 2024, 41(11): 1455-1463.] DOI: 10.16190/j.cnki.45-1211/r.2024.11.002.

5. 郝运, 李川, 文天夫, 等. 全球及中国的肝癌流行病学特征: 基于《2022全球癌症统计报告》解读[J]. 中国普外基础与临床杂志, 2024, 31(7): 781-789. [Hao Y, Li C, Wen TF, et al. Epidemiological characteristics of liver cancer worldwide and in China: an interpretation of global cancer statistics 2022[J]. Chinese Journal of Bases and Clinics in General Surgery, 2024, 31(7): 781-789.] DOI: 10.7507/1007-9424.202405099.

6. Filho AM, Laversanne M, Ferlay J, et al. The GLOBOCAN 2022 cancer estimates: data sources, methods, and a snapshot of the cancer burden worldwide[J]. Int J Cancer, 2025, 156(7): 1336-1346. DOI: 10.1002/ijc.35278.

7. Fu J, Wang H. Precision diagnosis and treatment of liver cancer in China[J]. Cancer Lett, 2018, 412: 283-288. DOI: 10.1016/j.canlet.2017.10.008.

8. Serper M, Taddei TH, Mehta R, et al. Association of provider specialty and multidisciplinary care with hepatocellular carcinoma treatment and mortality[J]. Gastroenterology, 2017, 152(8): 1954-1964. DOI: 10.1053/j.gastro.2017.02.040.

9. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019[J]. CA Cancer J Clin, 2019, 69(1): 7-34. DOI: 10.3322/caac.21551.

10. Wang Z, Wu L, Zhou Y, et al. Protein and metabolic profiles of tyrosine kinase inhibitors co-resistant liver cancer cells[J]. Front Pharmacol, 2024, 15: 1394241. DOI: 10.3389/fphar.2024.1394241.

11. Liu R, Li HF, Li S. PD-1-mediated inhibition of T cell activation: mechanisms and strategies for cancer combination immunotherapy[J]. Cell Insight, 2024, 3(2): 100146. DOI: 10.1016/j.cellin.2024.100146.

12. Wang C, Yang L, Xu S, et al. Systematic analysis of the role and significance of target genes of active ingredients of traditional Chinese medicine injections in the progression and immune microenvironment of hepatocellular carcinoma[J]. Front Pharmacol, 2022, 13: 1095965. DOI: 10.3389/fphar.2022.1095965.

13. Li X, Huang Y, He Y, et al. Wogonoside alleviates the proliferation and promotes the apoptosis in liver cancer cells by regulating PI3K/Akt signaling pathway[J]. Discov Oncol, 2025, 16(1): 244. DOI: 10.1007/s12672-025-01995-5.

14. Bai C, Zhao J, Su J, et al. Curcumin induces mitochondrial apoptosis in human hepatoma cells through BCLAF1-mediated modulation of PI3K/AKT/GSK-3β signaling[J]. Life Sci, 2022, 306: 120804. DOI: 10.1016/j.lfs.2022.120804.

15. Ji D, Chen Y, Bi J, et al. Entecavir plus Biejia-Ruangan compound reduces the risk of hepatocellular carcinoma in Chinese patients with chronic hepatitis B[J]. J Hepatol, 2022, 77(6): 1515-1524. DOI: 10.1016/j.jhep.2022.07.018.

16. Yang X, Feng Y, Liu Y, et al. Fuzheng Jiedu Xiaoji formulation inhibits hepatocellular carcinoma progression in patients by targeting the AKT/CyclinD1/p21/p27 pathway[J]. Phytomedicine, 2021, 87: 153575. DOI: 10.1016/j.phymed.2021.153575.

17. Chen G, Li J, Cai Y, et al. A glycyrrhetinic acid-modified curcumin supramolecular hydrogel for liver tumor targeting therapy[J]. Sci Rep, 2017, 7: 44210. DOI: 10.1038/srep44210.

18. Ninkov A, Frank JR, Maggio LA. Bibliometrics: methods for studying academic publishing[J]. Perspect Med Educ, 2022, 11(3): 173-176. DOI: 10.1007/s40037-021-00695-4.

19. Cooper ID. Bibliometrics basics[J]. J Med Libr Assoc, 2015, 103(4): 217-218. DOI: 10.3163/1536-5050.103.4.013.

20. Chen C, Song M. Visualizing a field of research: a methodology of systematic scientometric reviews[J]. PLoS One, 2019, 14(10): e0223994. DOI: 10.1371/journal.pone.0223994.

21. Van Eck NJ, Waltman L. Software survey: VOSviewer, a computer program for bibliometric mapping[J]. Scientometrics, 2010, 84(2): 523-538. DOI: 10.1007/s11192-009-0146-3.

22. Wu Z, Chen S, Wang Y, et al. Current perspectives and trend of computer-aided drug design: a review and bibliometric analysis[J]. Int J Surg, 2024, 110(6): 3848-3878. DOI: 10.1097/js9.0000000000001289.

23. 李锴, 孙航, 吴传新. 中药复方注射液在肝癌治疗中的研究进展[J]. 中华肝脏病杂志, 2022, 30(9): 1007-1011. [Li  K, Sun  H, Wu CX. Research progress of compound injection of traditional Chinese medicine in the treatment of liver cancer[J]. Chinese Journal of Hepatology, 2022, 30(9): 1007-1011. DOI: 10.3760/cma.j.cn501113-20210927-00486.

24. Ding Z, Wang L, Sun J, et al. Hepatocellular carcinoma: pathogenesis, molecular mechanisms, and treatment advances[J]. Front Oncol. 2025, 15: 1526206. DOI: 10.3389/fonc.2025.1526206.

25. Hu B, An HM, Yan X, et al. Traditional Chinese medicine formulation Yanggan Jiedu Sanjie inhibits TGF-β1-induced epithelial-mesenchymal transition and metastatic potential in human hepatocarcinoma Bel-7402 cells[J]. BMC Complement Altern Med, 2019, 19(1): 67. DOI: 10.1186/s12906-019-2477-9.

26. Xu F, Bai L, Dai Z, et al. Research hotspots and trends in post-stroke dysphagia: a bibliometric analysis[J]. Front Neurosci, 2023, 17: 1275748. DOI: 10.3389/fnins.2023.1275748.

27. Chan JY, Tang PM, Hon PM, et al. Pheophorbide a, a major antitumor component purified from Scutellaria barbata, induces apoptosis in human hepatocellular carcinoma cells[J]. Planta Med, 2006, 72(1): 28-33. DOI: 10.1055/s-2005-873149.

28. Anwanwan D, Singh SK, Singh S, et al. Challenges in liver cancer and possible treatment approaches[J]. Biochim Biophys Acta Rev Cancer, 2020, 1873(1): 188314. DOI: 10.1016/j.bbcan.2019.188314.

29. Liu X, Li M, Wang X, et al. Effects of adjuvant traditional Chinese medicine therapy on long-term survival in patients with hepatocellular carcinoma[J]. Phytomedicine, 2019, 62: 152930. DOI: 10.1016/j.phymed.2019.152930.

30. Llovet JM, Kelley RK, Villanueva A, et al. Hepatocellular carcinoma[J]. Nat Rev Dis Primers, 2021, 7(1): 6. DOI: 10.1038/s41572-020-00240-3.

31. Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2): 115-132. DOI: 10.3322/caac.21338.

32. Liu J, Zhu M, Shi R, et al. Radix Sophorae Flavescentis for chronic hepatitis B: a systematic review of randomized trials[J]. Am J Chin Med, 2003, 31(3): 337-354. DOI: 10.1142/s0192415x03001107.

33. Adams JM, Cory S. The Bcl-2 apoptotic switch in cancer development and therapy[J]. Oncogene, 2007, 26(9): 1324-1337. DOI: 10.1038/sj.onc.1210220.

34. Xu Z, Dang Y, Chen X, et al. Quercetin 7-rhamnoside from Sorbaria sorbifolia exerts anti-hepatocellular carcinoma effect via DHRS13/apoptotic pathway[J]. Phytomedicine, 2024, 135: 156031. DOI: 10.1016/j.phymed.2024.156031.

35. Abdallah RH, Al-Attar AR, Shehata YM, et al. Comprehensive chemical profiling and mechanistic insight into anticancer activity of annona muricata leaves extract[J]. Pharmaceuticals (Basel), 2024, 17(5): 614. DOI: 10.3390/ph17050614.

36. Wang F, Mai J, Wang H, et al. Identification of Erzhu Jiedu recipe and its molecular mechanism underlying inhibited human hepatoma cells by UHPLC-Q-exactive orbitrap HRMS and network pharmacology[J]. J Ethnopharmacol, 2024, 325: 117893. DOI: 10.1016/j.jep.2024.117893.

37. Jin Q, Jiao W, Lian Y, et al. Study on antihepatocellular carcinoma effect of 6-shogaol and curcumin through network-based pharmacological and cellular assay[J]. Front Pharmacol, 2024, 15: 1367417. DOI: 10.3389/fphar.2024.1367417.

38. Zhang J, Liu Y, Wang X, et al. Curcumin inhibits proliferation of hepatocellular carcinoma cells by blocking PTPN1 and PTPN11 expression[J]. Oncol Lett, 2023, 26(1): 307. DOI: 10.3892/ol.2023.13893.

39. 宋雨馨, 池秀莲, 易悦, 等. “一带一路”国家及地区药用植物资源及其可利用性初探[J]. 中国中药杂志, 2024, 49(5): 1137-1143. [Song YX, Chi XL, Yi Y, et al. Resources and utilization of medicinal plants in countries and regions involved in "the Belt and Road" Initiative[J]. China Journal of Chinese Materia Medica, 2024, 49(5): 1137-1143.] DOI: 10.19540/j.cnki.cjcmm.20231129.102.

40. Celis JE, Heitor M. Towards a mission-oriented approach to cancer in Europe: an unmet need in cancer research policy[J]. Mol Oncol, 2019, 13(3): 502-510. DOI: 10.1002/1878-0261.12452.

41. Jiang S, Bao H. Exploring the mechanism of esculetin extracted from Chroogomphus rutilus in treating liver cancer based on network pharmacology, molecular docking, and in vivo experimental validation[J]. J Ethnopharmacol, 2025, 348: 119837. DOI: 10.1016/j.jep.2025.119837.

42. Yamada N, Matsushima-Nishiwaki R, Kozawa O. Quercetin suppresses the migration of hepatocellular carcinoma cells stimulated by hepatocyte growth factor or transforming growth factor-α: attenuation of AKT signaling pathway[J]. Arch Biochem Biophys, 2020, 682: 108296. DOI: 10.1016/j.abb.2020.108296.

43. Wu L, Li J, Liu T, et al. Quercetin shows anti-tumor effect in hepatocellular carcinoma LM3 cells by abrogating JAK2/STAT3 signaling pathway[J]. Cancer Med, 2019, 8(10): 4806-4820. DOI: 10.1002/cam4.2388.

44. Zhang J, Guo J, Qian Y, et al. Quercetin induces apoptosis through downregulating P4HA2 and inhibiting the PI3K/Akt/mTOR axis in hepatocellular carcinoma cells: an in vitro study[J]. Cancer Rep (Hoboken), 2025, 8(5): e70220. DOI: 10.1002/cnr2.70220.

45. Cai C, Liu K, Yang D, et al. The nanocrystal-loaded liposome of tanshinone IIA with high drug loading and stability towards efficient liver fibrosis reversion[J]. Nanomedicine, 2025, 63: 102797. DOI: 10.1016/j.nano.2024.102797.

46. Cao X, Wang B. Targeted PD-L1 PLGA/liposomes-mediated luteolin therapy for effective liver cancer cell treatment[J]. J Biomater Appl, 2021, 36(5): 843-850. DOI: 10.1177/08853282211017701.

47. Farooq MA, Trevaskis NL. TPGS decorated liposomes as multifunctional nano-delivery systems[J]. Pharm Res, 2023, 40(1): 245-263. DOI: 10.1007/s11095-022-03424-6.

48. Xu Y, Wang M, Ning S, et al. Development of glycyrrhetinic acid and folate modified cantharidin loaded solid lipid nanoparticles for targeting hepatocellular carcinoma[J]. Molecules, 2022, 27(20): 6786. DOI: 10.3390/molecules27206786.

49. Song B, Shuang L, Zhang S, et al. Research progress of nano drug delivery systems in the anti-tumor treatment of traditional Chinese medicine monomers[J]. PeerJ, 2025, 13: e19332. DOI: 10.7717/peerj.19332.

50. Sun Y, Li D, Yu Y, et al. Insights into the role of natural polysaccharide-based hydrogel wound dressings in biomedical applications[J]. Gels, 2022, 8(10): 646. DOI: 10.3390/gels8100646.

51. NCT04000737. YIV-906 (formerly PHY906/​KD018) with sorafenib in HBV(+) hepatocellular carcinoma (HCC)[EB/OL]. (2025-04-13) [2025-10-25]. https://clinicaltrials.gov/study/NCT04000737?cond=NCT04000737&rank=1.

52. NCT05903456. Icaritin soft capsule combined with lenvatinib and TACE for the treatment of hepatocellular carcinoma[EB/OL]. (2023-06-15) [2025-10-21]. https://clinicaltrials.gov/study/NCT05903456?cond=NCT05903456&rank=1.

53. NCT03236636. Comparison of efficacy and safety of icaritin versus cinobufotalin in first-line treatment of advanced hepatocellular carcinoma subjects: a multicenter, randomized, double-blind, double-dummy phase III clinical trial[EB/OL]. (2021-01-27) [2025-10-21]. https://clinicaltrials.gov/study/NCT03236636?cond=NCT03236636&rank=1.