Nanotechnology is considered a new technology playing an essential role in several science fields. Titanium dioxide nanoparticles (TiO2 NPs) are extensively utilized inseveral fields like electronics, medicine, agriculture, food additives, paint, and sunscreens. Oral exposure mainly occurs through food products containing TiO2 NPadditives. Therefore, exposure to TiO2 NPs orally may have some adverse effects on exposed mammals and thus might be in potential health risk. The current study aims to study the possibility of liver damage in male rats exposed to a single oral dose (250 mg/kg b.w.) of 25 ± 5 TiO2 NPs. The gene expression of oxidative stress genes (Gpx and Cu-Zn SOD), protein folding gene (Hsp70), apoptosis gene (p53), metal toxicity gene (Mt1) as target genes, and GAPDH as housekeeping genes were determined. The results indicated that significant over-expression of the oxidative stress, apoptosis and protein folding genes was observed in the liver at 7 days post -treatment while there were no significant changes at day 28 as compared with control. Meanwhile, expression of the metal toxicity gene was increased significantly at both 7 and 28 days after exposure.Based on the abovementioned observation, it should be considered to possible health risks associated with the consumption of food products containing high concentrations of TiO2 NP-additives.