Objective:To investigate the effects of siRNA of ADAM17 gene and genistein on apoptosis and the inhibition of proliferation in HepG2 cells in an attempt to seek an effective therapy for hepatocellular carinoma. Methods:Cells were divided into control groups and experimental groups and siRNA was used to silence the ADAM17 gene, alone and in combination with genistein. Cells were harvested at several time periods and assessed for proliferation and apoptosis. Proliferation was assayed by MTT at 24, 48, 72 and 96 hours following treatment and apoptosis was assessed by flow cytometric analysis at 48 hours. Results:In siRNA groups, proliferation of cells was significantly inhibited compared to the control groups at 24, 48 and 72 hours(P < 0.05), and apoptosis was significantly increased at 48 hours(P < 0.01); In genistein groups, proliferation was inhibited at 24, 48, 72 and 96 hours, and the apoptosis ratio was significantly increased at 48 hours(P < 0.01); while in the groups that received the combination of siRNA transfection and genistein treatment, there was a further significant decrease of proliferation and increase in apoptosis compared with either treatment alone. Conclusion:The ADAM17 gene could be an effective target, and genistein could be a useful agent, in the treatment of hepatocellular carcinoma. siRNA of ADAM17 gene and genistein both inhibited HepG2 cells proliferation and promoted apoptosis, and further, the combination of these treatments had a greater effect than either treatment alone.