Abstract: To observe the inhibitory effect of APE1 siRNA generated by vector pSilence in conjunction with local radiotherapy on osteosarcoma cells of nude tumor- bearing mice. Methods: Thirty nude mice inoculated with 9901 osteosarcoma cells were randomly divided into 3 groups: the control group, the radiotherapy group and the group that received pSilence APE1 therapy plus radiotherapy. On the 15th day of the experimental treatment, the mice were sacrificed and the tumor growth curve was plotted. Meanwhile, the expression of APE1 protein and intratumor microvessel density (MVD) were observed by immunohistochemistry. The apoptotic index was detected by the Terminal dUTP nick end labeling (TUNEL) technique. Results: There was a significant difference in tumor volume among the group of pSilence APE1 plus simple radiotherapy, the control group and the radiotherapy group (P<0.05). The APE1 expression in the tumor cells in the group of pSilence APE1 plus simple radiotherapy was significantly decreased. The intratumoral microvessel density (MVD) in the group of pSilence APE1 plus simple radiotherapy was significantly lower compared to the control group and the radiotherapy group (P<0.01), while the apoptosis index was much higher (P<0.01). Conclusion: Using pSilence APE1 in conjunction with radiotherapy can significantly inhibit the growth of osteosarcoma.