Ionizing radiation induces DNA damage on normal cell results in apoptosis and cell deaths. The radioprotective effects of cerium oxide nanoparticles (CNPs) on genotoxicity, apoptosis and necrosis induced by Ionizing Radiation (IR) in human healthy lymphocytes as highly radiosensitive cells were investigated. Lymphocytes were prepared from three volunteers and then treated with CNPs at different concentrations and exposed to IR at dose 1.5 Gy. The radioprotective effects of CNPs were assessed by micronucleus (MN) assay and flow cytometry. Interleukin-1 was quantified in treated samples. It was found that CNPs reduced the percentage of MN induced by IR in lymphocytes up to 73%. CNPs treatment significantly reduced IR-induced apoptotic and necrotic incidences in human lymphocytes. CNPs significantly reduced IL-1β produced in cell environment exposed to IR. The present study demonstrated that CNPs may be an effective radioprotector against DNA damage and apoptosis induced by IR mainly through mitigation of pro-inflammatory process in lymphocytes. This result provides a new potential indication of CNPs for protection of normal cells during radiation therapy in the treatment of cancer or unwanted radiation exposure.