The increasing application of titanium dioxide nanoparticles (NTiO2) in life and the toxicity potential of these nanoparticles have raised concerns about their detrimental effects on human health. This study was conducted to investigate the hepatoprotective effects of vitamin E and vitamin A against hepatotoxicity induced by NTiO2 in rats. Thirty-six male Wistar rats were randomly divided into six groups of six rats each. Intoxicated group received 300 mg/kg NTiO2 for two weeks by gavage. Groups treated with vitamin E (100 IU/kg), vitamin A (100 IU/kg) and mixture of these vitamins were orally administered for 3 weeks (started 7 days before NTiO2 administration). In order to investigate the redox changes, total antioxidant capacity, total oxidant status, and lipid peroxidation were determined in liver tissue as well as activity of antioxidant enzymes including superoxide dismutase, glutathione peroxidase, and catalase. In addition, inflammatory responses were assessed by measuring the expression of NF-κB (mRNA) and TNF-α (mRNA and protein). Histopathological analysis and measurement of liver enzymes (ALP, ALT, AST, and LDH in serum) were also done to determine hepatic injury. In liver, NTiO2 caused hepatic injury, redox perturbation, and reduction of antioxidant enzymes and elevation of inflammatory mediators, significantly. However, treatment with vitamins was able to significantly ameliorate these alterations. This study highlights the antioxidant and anti-inflammatory properties of vitamins A and E against toxicity of NTiO2 and poses the use of these vitamins to mitigate the toxic effects of this nanoparticles in NTiO2-contained products.