Reactive oxygen species (ROS) are toxic substances produced during metabolic processes and also generated by exogenous sources, such as ionizing radiation and various chemical oxidants. ROS produced in living organisms are highly reactive and damage lipids, proteins and DNA. ROS-mediated DNA damage contributes to spontaneous mutagenesis. The oxidation of DNA results in various functional disorders, including premature aging and cancer. Recently, the oxidation resistance-1 (OXR-1) gene was identified in eukaryotic cells and was shown to be involved in protection against oxidative stress. However, its function still remains uncertain. In this study, 1) we cloned the human OXR1 and C. elegans CeOXR genes and examined whether these proteins could complement the spontaneous mutations in E. coli mutM mutY mutant. The double mutant showed a high spontaneous mutation frequency. We found that E. coli mutM mutY mutants expressing the cloned OXR1 and CeOXR proteins showed significantly decreased mutation frequency. 2) Yeast oxr1 mutant showed highly sensitive to H2O2 and MMS. 3) Human OXR1 protein was induced by H2O2 and MMS. Furthermore, we compared the lifespan of C. elegans oxr-1 mutant with that of wild-type strain N2. The lifespan of oxr-1 mutant was shortened compare with that of wild-type N2. Thus, CeOXR-1 may function to extend lifespan by suppressing the oxidative stress inC. elegans.