In this study, the protective effects of antioxidant quercetin(QCT) were studied on indices of oxidative stress, liver enzymes activity and the expression of cytochrome P450 1A1 (CYP1A1) against hepatotoxicity induced by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) in male rat. Thirty adult male Wistar rats randomly divided into five equal groups. TCDD and QCT were orally administered at the dose of 10µg/kg /day and 20 mg/kg/day, respectively by gavage dissolved in corn oil for 90 days. At the end of the study, animals were sacrificed and their liver were removed for biochemical analysis including the level of oxidative stress biomarkers, liver enzymes, and the expression of CYP1A1 gene. The results of this study indicated that exposure to TCDD (10µg/kg/day) could significantly increase liver oxidative stress biomarkers and serum liver enzymes (p<0.05). While, pre and post treatment of QCT (20 mg/kg/day) had protective effects on hepatotoxicity induced by TCDD and could significantly decrease these factors (p<0.05). Furthermore, there is no difference between the pre and post treatment of QCT (p>0.05). In addition to, the results showed that prolonged exposure to TCDD causes mutation in CYP1A1 gene and increases the expression of this gene in liver cells, while these effects were not observed in the pre and post treatment of QCT in rats treated with TCDD. The results showed that exposure to TCDD for 90 consecutive days could cause liver damage by oxidative stress, genotoxicity effect and alteration in the expression of CYP1A1 gene, and quercetin was able to cure these damages.