Tumor hypoxia is known to be one of the vital factors that aggravate tumor resistance to radiation therapy (RT) in which oxygen plays a critical role in tumor destruction. Herein, we synthesize a simple nanoradiosensitizer based on ultrathin BiO2-x nanosheets (NSs) modified with Tween 20 (T-BiO2-x NSs) to overcome the hypoxia-induced radioresistance as well as increase the efficacy of RT. On the one hand, bismuth as a high-Z element can effectively enhance the sensitivity of RT by depositing a higher radiation dose in tumors. The semiconductor property also endows its photocatalytic ability to produce extra reactive oxygen species (ROS) by reaction with the surrounding water. On the other hand, the defect-abundant BiO2-x NSs are also found to decompose the highly expressed hydrogen peroxide (H2O2) at the tumor site into oxygen (O2) for combating hypoxia. Both in vitro and in vivo experiments indicate that the as-prepared T-BiO2-x NSs could effectively inhibit tumor growth with X-ray irradiation. Our work thus provides a simple nanoradiosensitizer with multifunctionalities for increasing the RT efficacy while alleviating tumor hypoxia at the same time.