The extensive application of titanium dioxide nanoparticles (TiO₂ NPs) in the food industry arouses a debate regarding the probable risk associated with their use. Several recent studies reported that most nanoparticles (NPs) have adverse actions on the liver. The objective of this study is to examine whether Tiron plays a modulatory role against apoptotic damage induced by TiO₂ NPs in rat livers. Forty rats were randomly divided into 4 groups; a control group received phosphate-buffered saline, an intoxicated group received 100 mg/kg/day of TiO₂ NPs for 60 days, a treated group received 470 mg/kg/day of Tiron for the last 14 days after TiO₂ NPs administration, and a Tiron group received Tiron only as previously mentioned. Oral administration of TiO₂ NPs significantly increased serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP). In the liver, TiO₂ NPs increased oxidative stress through increasing lipid peroxidation and decreasing GSH concentration and the levels of the SOD and GPx enzymes. TiO₂ NPs significantly upregulated the proapoptotic Bax gene and downregulated the antiapoptotic Bcl-2 gene. Histopathological examination of hepatic tissue reinforced the previous biochemical results. Apoptotic lesions were also obvious in this group. Treatment with Tiron as an antioxidant significantly decreased serum biochemistry, ameliorated oxidative stress in hepatic tissue, upregulated Bcl-2, decreased Bax expression and attenuated the histopathology of hepatic injury. These findings indicate that Tiron effectively diminishes the hazardous effects of TiO₂ NPs on rat liver.