OBJECTIVE： To study induction effect of entecavir on the apoptosis of hepatocellular carcinoma HepG2 cells and its mechanism. METHODS： After treated with 0 （normal control）， 10， 30 and 100 μmol/L （low， medium and high concentration groups） entecavir for 48 h， MTT method was adopted to detect HepG2 cell viability. AnnexinⅤ-PI flow double staining was used to detect cell apoptosis. Western blot was used to determine the phosphorylation of nuclear factor kappa B p65 （NF-κB p65） and nuclear factor kappa B inhibitor α （IκBα）， and the protein expression of Bax， Bcl-2， Survivin and C-myc.  RESULTS： Compared with normal control group， the cell viability， the phosphorylation of NF-κB p65 and IκBα， and the protein expression of Survivin， C-myc and Bcl-2 of entecavir low， medium and high concentration groups all decreased； the apoptotic rate， the protein expression of Bax increased （P＜0.05 or P＜0.01）， in concentration-dependent manner. CONCLUSIONS： Entecavir can decrease viability of HepG2 cells and induce cell apoptosis， which is related to up-regulation expression of Bax， down-regulation expression of Survivin， C-myc and Bcl-2， and blocking the activation of NF-κB/IκBα signaling pathway.