To explore the role of apolipoprotein M(ApoM) and mitochondrial apoptosis in liver cancer，and the potential mechanism of ginsenoside Rb1 in affecting liver cancer through the ApoM/mitochondrial apoptosis pathway.Methods:Bioinformatics analysis was used to screen for differential expression of ApoM in liver cancer，followed by clinical validation.Molecular docking determined the targeted binding of ginsenoside Rb1 to ApoM.Human liver cancer cells(HepG2) were cultured in vitro，and cell viability was assessed using the CCK-8 assay to screen for the optimal intervention concentration of ginsenoside Rb1.Clonogenic assays were conducted to evaluate HepG2 cell proliferation，while scratch assays were used to assess the migration ability of HepG2 cells.Protein expression of ApoM and apoptosis-related genes，including Bax，Bcl2，Caspase-3，and Caspase-9，was detected using Western blot.Real-time quantitative PCR(RT-qPCR) was employed to measure mRNA expression levels of ApoM and apoptosis-related genes(Bax，Bcl2，Caspase-3，and Caspase-9).Results:Survival analysis indicated that low ApoM expression correlated with poorer prognosis in liver cancer.Molecular docking suggested a high affinity between ginsenoside Rb1 and ApoM.Clonogenic and scratch assays indicated that ginsenoside Rb1 effectively inhibited HepG2 cell proliferation.Western blot and RT-qPCR confirmed that ginsenoside Rb1 modulated the protein and mRNA expression of mitochondrial apoptosis-related genes.Conclusion:This study reveals the important role of the ApoM/mitochondrial apoptosis pathway in liver cancer，suggesting that ginsenoside Rb1 may influence liver cancer through the ApoM/mitochondrial apoptosis pathway.