Objective: To reveal the regulatory role of Hederagenin on IL-6 and its possible immune mechanism for inhibiting the proliferation of hepatocellular carcinoma cells. Methods: ①Bioinformatics was used to analyze the immune pathways regulated by IL-6: the GEO2R tool was used to analyse differentially expressed genes in GeneChip dataset GSE14632 and the Immport database was used to download immune genes, intersecting genes were screened between differentially expressed genes and immune genes. The KOBAS database was used to perform KEGG enrichment analysis of intersecting genes. ②Experimental validation of the regulation of IL-6 by HD: Western blot was used to detect the relative expression of IL-6 protein in HepG2 cells under HD( 0, 30, 60 and 120 μg/ml) intervention. H22 tumour-bearing mice were randomly divided into 5 groups, 12 cases in each group: control group; CTX group, 25 mg/kg; HD low dose group, 100 mg/kg; HD medium dose group, 200 mg/kg; HD high dose group, 400 mg/kg. Mice were administered intraperitoneally for 14 days. On day 15, all animals were weighed and executed and the tumours were removed. Western blot was used to detect the relative expression of IL-6, KRAS, RAF1, MEK2, p-ERK1/2, p-JNK, AKT, NF-κB p50, PD-L1 and p-STAT3 proteins in the tumours of each group. Results: Bioinformatics analysis revealed that MAPK signaling pathway, PD-L1 expression and PD-1 checkpoint pathway were regulated by IL-6; the result of in vitro experiment showed that the relative protein expression of IL-6 in HD( 30, 60 and 120 μg/ml) intervention groups showed a decreasing trend compared to control group( P<0.01); the results of in vivo experiment showed that the relative proteins expression of IL-6, KRAS, RAF1, MEK2, p-ERK1/2, p-JNK, AKT, NF-κB p50, PD-L1 and p-STAT3 in HD (100, 200 and 400 mg/kg) intervention groups showed an overall decreasing trend compared to control group (P<0.01). Conclusion: HD may regulate the activity of PD-1/PD-L1 and MAPK immune signaling pathways in liver cancer cells by inhibiting the expression of IL-6 protein, resulting in the damage of adaptive immune response of liver cancer, thereby inhibiting the proliferation of cancer cells. [ABSTRACT FROM AUTHOR]