Radiotherapy is one of the main therapeutic methods for cancers, but radiation resistance of cancer cells still remains a serious concern. Searching for radiosensitizers to overcome such resistance is therefore urgently required. The goal of this study is to evaluate and compare the radiosensitizing efficacy of FeO-OA, Ag and FeO@Ag nanoparticles on U251 cells. The results show that FeO@Ag nanoparticles have the highest ability of radiosensitization among the three nanoparticles. The underlying mechanism of FeO@Ag nanoparticles' radiosensitivity enhancement is through decrease of the cytoprotective autophagy at the early stage, and increase of the calcium-dependent apoptosis at the later stage. These findings suggest the potential application of FeO@Ag nanoparticles as a highly effective nano-radiosensitizer for the treatment of glioblastoma cells.