Aim To investigate the antitumor and antiangiogenic effects of combined low-dose cyclophosphamide(CTX)and recombined VEGF protein vaccine.Methods In this experiment,H22 hepatocellular carcinoma model was established in BALB/c mice.Mice were randomly divided into four groups: control group,CTX group(CTX),VEGF protein vaccine group(V2)and CTX plus V2 group(CTX+V2).The anti-tumor efficacy and antiangiogenic effect were investigated using a subcutaneous tumor model and an intradermal tumor model.Western blot and ELISAwere further adopted to detect the specific anti-VEGF antibody.Results CTX+V2 group displayed a lower tumor volume and tumor weight than either the single therapy group in the subcutaneous tumor model(P<005 vs V2,P<001 vs CTX).Meanwhile,CTX+V2 was more effective for antagonizing tumor-associated angiogenesis compared with either the single therapy(P<005 vs V2,P<001 vs CTX).After CTX+V2 immunization,high titer of anti-VEGF antibody was detected by ELISA and verified by Western blot.Conclusion The therapy of CTX combined with V2 has significant synergistic effect against H22 hepatocellular carcinoma.