Owing to their radical scavenging and UV-filtering properties, ceria nanoparticles (CeO(2)-NPs) are currently used for various applications, including as catalysts in diesel particulate filters. Because of their ability to filter UV light, CeO(2)-NPs have garnered significant interest in the medical field and, consequently, are poised for use in various applications. The aim of this work was to investigate the effects of short-term (24 h) and long-term (10 days) CeO(2)-NP exposure to A549, CaCo2 and HepG2 cell lines. Cytotoxicity assays tested CeO(2)-NPs over a concentration range of 0.5 μg/mL to 5000 μg/mL, whereas genotoxicity assays tested CeO(2)-NPs over a concentration range of 0.5 μg/mL to 5000 μg/mL. In vitro assays showed almost no short-term exposure toxicity on any of the tested cell lines. Conversely, long-term CeO(2)-NP exposure proved toxic for all tested cell lines. NP genotoxicity was detectable even at 24-h exposure. HepG2 was the most sensitive cell line overall; however, the A549 line was most sensitive to the lowest concentration tested. Moreover, the results confirmed the ceria nanoparticles' capacity to protect cells when they are exposed to well-known oxidants such as H(2)O(2). A Comet assay was performed in the presence of both H(2)O(2) and CeO(2)-NPs. When hydrogen peroxide was maintained at 25 μM, NPs at 0.5 μg/mL, 50 μg/mL, and 500 μg/mL protected the cells from oxidative damage. Thus, the NPs prevented H(2)O(2)-induced genotoxic damage.