Malignant melanoma is characterized by high degree of malignancy, early metastasis and high mortality. However, it is indicated by clinical experience that malignant melanoma is resistant to conventional radiotherapy. Therefore, it is of great significance to radiosensitize melanoma cells in the treatment of this kind of malignancy. In the present study, the melanoma cell lines with inducible RAC2 overexpression or RAC2 knockdown were established. The effect of RAC2 on radiosensitivity of melanoma cells were evaluated by colony formation assay and γH2AX assay. Meanwhile, the ROS yield and the NADPH oxidase activity were analyzed in the irradiated melanoma cells. We find that RAC2 overexpression sensitizes the melanoma cells by enhancing the NADPH oxidase activity and the subsequent ROS production. 