Background: The extensive use of nanoparticles in our life especially zinc oxide nanoparticles (ZnO NPs) in cosmetics, sun blockers, paints and food additives draw our attention toward their hepatotoxicity and the protective role of Qurecitin (QE).  Objective: the present study aimed to investigate the hepatotoxic effect of ZnONPs and the protective role of Qurecitin against it.  Results: I/P injection of ZnONPs in a dose of 200 and 400 mg/ kg b.wt resulted in a significant increase in the serum levels of ALT, ALT and ALP with a significant increase in the hepatic MDA levels and decrease in non-enzymatic (GSH) and Enzymatic (GPx, GR, SOD and CAT) activities and their mRNA levels. Meanwhile, the co-treatment of ZnONPs with QE ameliorate the hepatic condition through decreasing the liver enzymes and MDA with increase in the antioxidant levels and their gene expression.  Conclusion: Taken together it can be concluded that QE has an ameliorative effect against ZnONPs hepatotoxicity.