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Background: Radiotherapy is an important protocol in the treatment of cancers, but radioresistance of cancerous cells is a challenge in cancer treatment. Objective: The aim of this study was to evaluate the radiosensitizing effect of Cerium oxide Nanoparticles (CNPs) on human promyelocytic leukemia cells (HL-60). Method: HL-60 cells were treated with CNPs at different concentrations (10-100 μg/ml) and exposed to Ionizing Radiation (IR). The genotoxicity effects of CNPs or/and IR were assessed by micronuclei assay in HL-60 cells. Results: It was found that CNPs increased the frequencies of micronuclei in HL-60 cells. CNPs pretreatment to irradiation significantly increased the IR-induced micronuclei incidences in HL-60 cells. The present study demonstrates CNPs to be an effective sensitizer on DNA damage induced by IR in HL-60 cells. Conclusion: These findings suggest the potential application of CNPs as a highly effective radiosensitizer for the treatment of leukemia.