Background/aim: Doxorubicin (DOX) is a widely used and potent chemothe- rapeutic agent. However, serious dose-limiting toxicity through generation of free oxygen radicals is a commonly encountered clinical problem. The aim of the current study was to assess the protective role of onion (Allium cepa) extract (ACE) against DOX-induced hepatotoxicity in rats. Method: A total of 24 rats were randomly divided into 3 equal experi- mental groups: (1) DOX; (2) ACE + DOX; and (3) control groups. ACE was gi- ven orally as 1 mL of fresh ACE juice for 14 consecutive days followed by DOX injection. DOX was injected intraperitoneally in a single dose of 30 mg/kg body weight to induce hepatotoxicity, and the rats were killed after 48 h from injec- tion. Control group was given saline only. Results: In the ACE pretreated group (ACE + DOX), serum aspartate transaminase, alanine transaminase, and tissue malondialdehyde and gluta- thione levels were significantly lower, while superoxide dismutase and gluta- thione peroxidase were higher compared with the DOX group. The histopatho- logical examination of liver specimens revealed parenchymal necrosis, proli- feration of biliary duct in DOX group; while ACE pretreatment provided marked reduction in these changes. Conclusion: Our study indicates that pretreatment with ACE protects against DOX-induced hepatotoxicity due to the antioxidant properties of ACE. Further studies on efficacy of antioxidant treatment by ACE in DOX-mediated toxicity and underlying mechanisms would provide a better explanation.