Abstract: Objective To investigate the mechanism of Huaier Granules combined with Thalidomide inhibited tumor. Methods Male Kunming mice were randomly divided into controlled group(group A)，Huaier granules group (group B), Thalidomide group(group C), and Huaier granules plus Thalidomide group(group D).Each group consisted of 10 mice. The tumor-bearing mice model was induced by subcutaneously injection of H22 cells．The mass of transplanted tumor and inhibition rate of tumor in all groups were observed．The expression of VEGF and CD31 protein was assayed by immunohistochemical method． Results Compared with those in control group，the mass of transplanted tumor tissue and the positive rate of CD31 protein in three treated groups were significantly decreased(P＜0.01)．And the positive rate of VEGF protein in group D was significantly decreased(P＜0.01)．Compared with those in group A and group B，the mass of tumor tissue and the positive rate of CD31 protein in group D were significantly decreased(P＜0.05). Conclusion Huaier granules and Thalidomide had marked and synergy antitumor effect. The mechanism might be related to the apoptosis of tumor cells induced by the down-regulation of vascular endothelial growth factor(VEGF) protein.