Abstract: To observe the anti-tumor effect and the enhancement effect on chemotherapy of sildenafil and its possible mechanism. Methods Mice with S180 sarcoma were divided into groups randomly. The treated groups were administered low［30mg/（kg•d）］,moderate［60mg/（kg•d）］and high［100mg/（kg•d）］dose sildenafil separately or combined with cyclophophamide(CTX). The tumor- inhibitory rate was counted. Apoptosis and cell cycle of tumor cells in mice treated with medium dose sildenafil were detected with fluorescence microscopy at six day.The level of VEGF,p53,cAMP,cGMP of tumor cell in mice treated with medium dose sildenafil were detected by ELISA at six day. Results The tumor-inhibitory rate of co-chemotherapy group was higher than sildenafil groups,and both of them were higher than blank control group.The level of VEGF,p53 and cell cycle in tumor cell of sildenafil groups were no difference with blank control group,but the level of cGMP and apoptosis rate were higher than blank control group, the level of cAMP decreased in sildenafil group. Conclusion Sildenafil had the anti - tumor effect and the enhancement effect of chemotherapy.The mechanism was that it may induce tumor cell apoptosis,and was irrelevant with the change of cell cycle,VEGF and p53.