Background: The speedy growth of the nanotechnology industry has led to the wide-scale production and application of engineered nanoparticles(NPs). Aim: The aim of the study is to evaluate the toxicity of oral exposure to zinc oxide nano-particles (ZnO-NPs) on liver tissue of albino rats, and hepatoprotective effect of Naringenin (N) against such ZnO-NPs induced toxicity. Materials &Methods: ZnO-NPs were administered orally in two doses (125 mg or 300mg/Kg body weight/ day for 21 consecutive days) to rats. Co-administration of Naringenin (20mg/Kg body weight daily for three weeks to rats. In order to detect the protective effects of the studied antioxidants against n-ZnO induce hepatotoxicity, different biochemical parameters were investigated. Moreover, histopathological examination of liver tissue was performed. Results: Nano zinc oxide-induced hepatotoxicity was confirmed by the elevation in the levels of serum Aspartate transaminase (AST), Alanine transaminase (ALT), and alkaline phosphatase (ALP) were considered as biomarkers to indicate hepatotoxicity. Additionally, a significant increase in oxidative stress through the increase in lipid peroxidation marker Malondialdehyde (MDA), a significant decrease in Glutathion peroxidase (GPx) activity and a significant decrease in non-enzymatic antioxidant reduced glutathione (GSH) in liver tissue. Moreover, elevation in inflammatory gene expression of cytokines (Tumor Necrosis Factor alpha (TNFα), Interleukin-2 (IL-2) and Interleukin-6 (IL-6). These biochemical findings were supported by a histopathological examination of liver tissue. Conclusion: The data suggested that Naringenin protects the liver from the hepatotoxicity caused by ZnO-NPs.