Objective The aim of this study is to explore the effect of arsenic trioxide (As 2 O 3 ) on radiosensitivity in cervical carcinoma xenografts and the possible underlying mechanisms of vascular endothelial growth factor (VEGF) and Ku autoantigen protein p70 (Ku70). Methods The tumor-bearing C57BL/6mouse model was established by injecting U14 cervical carcinoma cells into the right infra-axillary dermis of 40 mice. The mice were randomized into four groups: (1) control group (peritoneal injection, 0.2 ml of 0.9% normal saline); (2) As 2 O 3 only group (peritoneal injection, 2.0 mg/kg, 0.2 ml As 2 O 3 ); (3) irradiation only group (peritoneal injection 0.9%NS, 0.2 ml+6 MeV electron beam, 10 Gy); and (4) As 2 O 3 + irradiation group (peritoneal injection, 2.0 mg/kg, 0.2 ml As 2 O 3 +6 MeV electron beam, 10 Gy). The mice were sacrificed 25 days after randomisation. U14 cervical tumors from the mice were harvested and weighed. Response to treatment using radiation and/or As 2 O 3 was evaluated by extent of inhibition (i.e., growth inhibition rate) of tumor growth. VEGF and Ku70 mRNA expression and protein levels were evaluated by RT-PCR and immunohistochemistry, respectively. Results As 2 O 3 + irradiation was found to significantly increase the inhibition of tumor growth. The growth inhibition rates in As 2 O 3 only, irradiation only, and As 2 O 3 + irradiated groups were 10.48%, 30.30%, and 73.15%, respectively (p <0.05). The combination also significantly downregulated the expression of VEGF and Ku70 in irradiated cervical carcinoma xenografts as compared to the control group, As 2 O 3 only group, or irradiation only group (p <0.05). Conclusions Arsenic trioxide effectively sensitizes the cervical carcinoma xenografts to ionizing irradiation. Downregulation of the expression of VEGF and Ku70 is likely to play an important role.