To explore the effects of lamivudine on cell proliferation of liver cancer and expressions of HBsAg, HBeAg, and MMP-9 in hepatoma cells. In the intervention group, HepG2.2.15 cells were cultured with lamivudine at 100, 200, and 300 μmol/L for 24 hours, 48 hours, and 72 hours. In the control group, HepG2.2.15 cells were cultured without lamivudine. MTT assay was used to assess the proliferative activity of cells after the intervention by lamivudine for 24 hours, 48 hours, and 72 hours. ELISA was used to measure the expression levels of HBsAg, HBeAg, and MMP-9 after the intervention by lamivudine for 48 hours and 72 hours. There was no significant difference between the intervention group and the control group in the proliferation activity of cells (p>0.05). After 48 hours and 72 hours of intervention by lamivudine, the expressions of MMP-9, HBsAg, and HBeAg in the control group were statistically lower than those in the intervention groups with lamivudine at 100 μmol/L, 200 μmol/L, and 300 μmol/L (p<0.05). The expressions of MMP-9, HBsAg, and HBeAg in HepG2.2.15 gradually decreased with the increase of intervention concentration and intervention time of lamivudine (p<0.05). Lamivudine cannot directly inhibit the proliferation of liver cancer cells, but it can reduce the expressions of MMP-9, HBsAg, and HBeAg in hepatoma cells, inhibit the replication of HBV disease in hepatoma cells, and suppress tumor growth.