Background: This study aimed to assess and compare the radioprotective and cytotoxic effects of various concentrations of cerium oxide nanoparticles (CONPs) in aqueous solution combined with sodium dodecyl sulphate (SDS) against high energy X-ray beams in Vero cells. Materials and Methods: The scanner electron microscopy (SEM) method was used to analyze the properties of CONPs. The cells were incubated with different concentrations of CONPs in aqueous solution combined with SDS. The non-toxic CONPs concentrations in Vero normal cells were determined using MTT assay. The cell’s uptake was measured by an UV/VIS absorption spectrophotometry. The cells were irradiated with different doses of 18 MV photon (1, 2, and 3 Gy), and their viabilities at various concentrations were measured to evaluate the radiation protection effects of CONPs. Results: The CONPs concentrations lower than 600 μg/ml were referred as non-toxic effects regarding MTT results. The 600 μg/ml was regarded as the highest radioprotection effect among the non-toxic concentrations (P-value˂0.05). The average percentage of cell viability improvement was estimated as 17, 23.61, and 27.21% for 1, 2, and 3 Gy doses, respectively, compared to the control group (with no CONPs). Pearson’s correlation coefficients between the CONPs concentration and cell viability were obtained as 0.96, 0.99, and 0.99 for 1, 2, and 3 Gy doses, respectively; showing that the increased concentration leads to an increase in higher radioprotection. Conclusion: The 600 μg/ml of CONPs aqueous solution combined with SDS, as a stable non-toxic concentration, has the highest radiation protection effect when exposed to high-energy photon beams. So, this concentration can be considered as an appropriate candidate of radioprotection for further research.