Objectives：To observe the effect of eukaryotic expression vectors coding IL-2 and IL-12 on immune responses induced by DNA immunization of HBV surface antigen（pCR3.1-S）in BABL/c(H-2d) and the protection against P815 mastocytoma cells stable expressing HBV surface antigen in mice after immunized with HBV gene vaccine.Methods：The immunization was performed by intramuscular injection,three weeks later,we directly inoculated P815-HBV-S into mice by subcutaneous injection .Tumor growth was measured every five days.Anti-HBs in serum was detected by ELISA and HBsAg specific cytotoxic T lymphocytes (CTLs) activity was measured by 51 Chromium release assay.Results：Eight weeks after immunization,the A value of mice serum in 450 nm and CTLs activity of mice codiog IL-2 and IL-12 eukaryotic expression vectors were significant higher(P<0.05) than that of mice intramuscular injected HBV-S DNA vaccine,these values are significant higher than that of mice injected pCR3.1(P<0.05).The spleen cells CTLs activity have decreased obviously after treated with anti-CD8+ monoclonal antibody and have no significant change after treated with anti-CD4+ monoclonal antibody.The HBV-S gene vaccine could evidently inhibit the tumor growth,prolong the survival period (>38.2 days) and improve the survival rate in mice.Conclusions：The DNA vaccine of HBV ( pCR3.1-S) had strong antigenicity in cellular and humoral immunity and had marked killing effect on HBV infected cells in vivo，which could be promoted by vector coding murine IL-2 or IL-12.CTLs activity was performed by CD8+ cells.