Objective To observe the effects of extracellular-signal regulated kinase (ERK) 1/2 inhibitor U0126 on hepatoma carcinoma cell proliferation and apoptosis. Methods Hepatoma SMMC-7721 cell strain was divided into blank control group and different concentrations of U0126 groups. The proliferation inhibition was measured by MTT assay. FCM was used to analyze the cell cycle distribution and apoptosis. Results U0126 obviously inhibited cell proliferation, induced cell apoptosis and G0/G1 phase cell cycle arrest. There were significant differences between control group and different concentrations of U0126 groups on cell proliferation and apoptosis (P<0.05, P<0.01). Conclusion Blocking ERK1/2 pathway may be an important treatment strategy for liver cancer.