Radiotherapy (RT) has been used clinically to overcome cancer in recent decades. However, the abnormal tumor microenvironment (TME), involving hypoxia, acidosis and a dense extracellular matrix, is found to be related to the resistance of tumors to RT. Herein, intelligent bovine serum albumin (BSA)-coated Bi2S3 and MnO2 (Bi2S3-MnO2) nanocomposites synthesized via biomineralization are capable of modulating the hypoxic TME effectively to enhance the efficacy of RT. After intravenous injection, the BSA-Bi2S3-MnO2 nanocomposites show efficient accumulation in tumors, where endogenous H2O2 can react with MnO2 to generate oxygen in situ, leading to increased tumor oxygenation to overcome the hypoxia-associated resistance to RT. Moreover, the photothermal effect induced by the BSA-Bi2S3-MnO2 nanocomposites further relieves hypoxia in the TME and, finally, synergistically improves the effects of RT. In this work, we present a simple strategy to fabricate intelligent therapeutic nanoparticles to improve therapeutic efficiency towards cervical cancer.