Background: Titanium dioxide nanoparticles (Tio2NP) are important due to their various applications; sterilization, keeping rust away, and depigmentation. Aim: This study was designed to investigate the hepatic toxicity of sub-chronic oral exposure to Tio2 NP in adult male Wistar rats and to assess the possible protective effect of beta carotene (BC). Material and methods: Ninety adult male Wistar rats were divided into nine equal groups; Group I kept without any treatment (negative control), group II saline received (positive control), group III received BC (10mg/kg/day), groups IV, V, VI which were administrated with 30, 50 and 70mg/kg/day of Tio2NPs, group VII, VIII, IX which were administrated BC(10mg/kg/day) then 30, 50 and 70mg/kg/day of Tio2NPs for 60 days orally. Serum levels of AST and ALT were estimated after 30 days and at the end of the experiment. Furthermore, oxidative stress markers in liver tissue, including MDA and SOD were estimated. Histopathological examination of the liver tissues by light microscopy was also performed. Results: The results revealed a significant statistical increase in the levels of specific markers AST and ALT in TiO2 NPs treated groups in comparison to controls at the end of the study. There was a significant statistical decrease in the AST activity in protected groups by BC compared to 50 and 70 mg/kg administrated TiO2 NPs Tio2treated groups after 30 days of the study. Also, TiO2 NPs induced a significant elevation of MDA and a significant decrease in the antioxidant enzyme SOD in liver tissue, which was ameliorated by the administration of BC. Also, significant histopathological changes were detected in the form of numerous vacuolated hepatocytes, congestion in the portal vein, dilated congested sinusoids, numerous degenerated hepatocytes, and periportal inflammatory cell infiltration. These changes were improved by BC. Conclusion: It can be concluded that sub-chronic oral exposure to Tio2 NPs induces oxidative stress, which produces hepatotoxicity in the rat liver, and that of BC has a hepatoprotective and potential antioxidant role against its toxic effects. From the previous results, raising public awareness about the proper handling of TiO2 NPs materials and further studies about the usefulness of BC are recommended.