The present study was directed to evaluate the toxic effects of orally administered titanium dioxide naonparticles (TiO2) on liver of male albino rats and to evaluate the ameliorative effects of N-acetylcysteine (NAC). Forty adult male albino rats were divided into 4 groups; control group, NAC group, TiO2 group and TiO2/ NAC group. Rats were administered either TiO2 (1200 mg kg −1 BW) or NAC (100 mg kg −1 BW) alone or together for 9 months. Blood was taken to evaluate serum changes in GPT, GOT and MDA levels. Liver tissues were examined for changes in MDA, GSH and changes in liver histopathology. Administration of TiO2 increased serum GPT, GOT and decreased MDA levels. Co-treatment of rats with NAC and TiO2 improved such significant changes induced by TiO2 alone. Moreover, significant time dependent increase in MDA and decrease in GSH levels in liver tissues were recorded. Liver histopathology showed vacuolar, hydropic degeneration and cell death of some hepatic cells. In conclusion, results confirmed the protective effect of NAC in amelioration of the biohazard effects induced by TiO2 in rats.