Nanoparticles (NPs) and nanoparticle-based materials have been increasingly used in various consumer and medical applications. However, investigations have disclosed that some NPs may generate toxic effects in different cell types and organisms. In this study, the cytotoxic and genotoxic potential of titanium dioxide (TiO2) and zinc oxide (ZnO) NPs were examined by using four genotoxicity tests, chromosome aberrations-CAs, sister chromatid exchange-SCE, micronucleus-MN, and comet, in human lymphocytes in vitro. The results showed that both NPs significantly increased the frequency of aberrant cells, CA/Cell, SCE, and DNA damage, and decreased mitotic index in some treatments. These results demonstrated that TiO2 and ZnO NPs induce genotoxic effects. Therefore, more detailed in vitro and in vivo experiments should be conducted for the safe usage of both NPs.