Wide uses of titanium dioxide (TiO2) nanoparticles in cosmetics, paints, toothpastes, sunscreens, food products, pharmaceuticals and nanomedical reagents increases human exposure and its risk. Thus this study was designed to investigate the possible protective effect of chlorophyllin (CHL) on nano-TiO2 induced genotoxicity and oxidative stress in mice. Male mice were exposed to single i.p. injection with each of three dose levels of nano-TiO2 (500, 1000 or 2000 mg/kg b.w) suspended in deionized water or CHL (200 mg/kg b.w.). Micronucleus and comet assays were carried out genotoxic endpoints. Moreover, oxidative stress was evaluated using five markers of oxidative damage to shed more light on its mechanism. A dose-dependent genotoxicity of nano TiO2 was evidenced by the observed significant elevations in micronuclei frequencies and DNA damage levels. The same end.-points indicated that TiO2 genotoxicity was significantly decreased after CHL coadministration. Moreover, CHL significantly decreased malondialdehyde level, and significantly increased reduced glutathione level and superoxide dismutase, catalase and glutathione peroxidase activities, which were significantly disrupted by TiO2 alone. In conclusion, the dose dependent nano-TiO2 induced genotoxicity was diminished by CHL co-administration via its free radicals scavenger ability.