Objective Virus-specific RNA interference (RNAi) is a powerful inhibitor of gene expression and replication of HBV. It is known to have high efficiency, specificity, and few side effects. We wanted to evaluate the effects of siRNA silencing HBV replication on the growth of hepatocellular carcinomatic(HCC) cells to find out an ideal method for treatment of HCC. Methods We transfected siRNA into HepG2.2. 15 cells (HCC cell inserting HBV gene) and detected the HBsAg and HBV DNA copies for evaluating the inhibitory effects of siRNA. Then we evaluated cell growth and self-renewal ability after transfection of siRNA by MTT. Results The HBsAg level and HBV DNA copies were reduced after the transfection of siRNA, the highest inhibition rate was 83.9%,while the inhibition rate of HBV DNA copies reached 73. 4%. The siRNA group's growth ability and self-renewal rate were lower than the control group in 5 days. Conclusion siRNA can effectively inhibit HBV replication and expression in HepG2.2.15 cells and silencing HBV replication can inhibit HepG2.2.15 cell's growth and self-renewal.