High doses of radiation can cause serious side effects and efficient radiosensitizers are urgently needed. To overcome this problem, we developed a biomimetic nanozyme system (CF) by coating pyrite (FeS₂) into tumor-derived exosomes for enhanced low-dose radiotherapy (RT). CF system give FeS₂ with immune escape and homologous targeting abilities. After administration, CF with both glutathione oxidase (GSH-OXD) and peroxidase (POD) activities can significantly lower the content of GSH in tumor tissues and catalyze intracellular hydrogen peroxide (H₂O₂) to produce a large amount of ·OH for intracellular redox homeostasis disruption and mitochondria destruction, thus reducing RT resistance. Experiments in vivo and in vitro showed that combining CF with RT (2 Gy) can provide a substantial suppression of tumor proliferation. This is the first attempt to use exosomes bionic FeS₂ nanozyme for realizing low-dose RT, which broaden the prospects of nanozymes. Graphical Abstract