Background: Most nanoparticles have adverse impacts on the liver, which is a vital body organ, by the induction of oxidative stress. Objectives: This study was designed to evaluate the hepatoprotective effects of quercetin (QCT) against the toxicity of nanoscale titanium dioxide (NTiO2) in Wistar rats. Methods: The present study was conducted on 32 adult female Wistar rats assigned into 4 groups of control, NTiO2 (50 mg/kg), NTiO2 + Quercetin (50 + 75 mg/kg), and Quercetin (75 mg/kg). The animals exposed to NTiO2 were administered by 50 mg/kg of NTiO2 for 21 days. The Quercetin + NTiO2 rats received Quercetin before exposing to NTiO2 for 7 days. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) of serum were considered indicators of the hepatotoxicity. The oxidative stress was assessed by measuring the activity of catalase (CAT) and superoxide dismutase (SOD) as well as the level of malondialdehyde (MDA) in the liver. TUNEL assay and histological changes were also assessed. Results: The NTiO2 significantly elevated the MDA level (P < 0.01), enhanced the serum biomarker levels, reduced the CAT (P < 0.01) and SOD (P < 0.01) activities. The NTiO2 also aggregated the red blood cells, and caused inflammatory cell infiltration, nuclear pyknosis and fat deposit in hepatocytes, as well as induced apoptosis in the liver tissue. Pretreatment with QCT quenched oxidative stress, attenuated the histological changes, elevated the CAT (P < 0.01) and SOD (P < 0.01) activities, normalized the serum biomarker levels and decreased apoptosis (P < 0.001). Conclusions: The QCT has an inhibitory impact on hepatotoxicity induced by nanoparticles in rats.