This study investigated the protective effect of fish oil (FO) on cisplatin (CP) toxicity in the rat liver. Twenty-eight rats were divided equally into four groups, with the first being a control group. The second group (CP group) was given 7 mg/kg of CP and the third group (FO group) was given 1 FO softgel/rat/day for 14 days. The rats in the fourth group (CP + FO group) were treated with both CP and FO at the above doses. CP treatment caused significant oxidative damage via an increase in thiobarbituric acid reactive substances (TBARS) and reduced antioxidant defenses through a decrease in the activities of catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), and glutathione peroxidase (GPx) in rat liver tissue. Also, CP caused histopathological abnormalities, including necrosis, in the liver tissue. However, concurrent FO treatment prevented the negative oxidative and histopathological effects of CP. In conclusion, CP treatment can cause hepatotoxicity in rats, but dietary supplementation with FO can attenuate the oxidative and histological changes caused by CP. Thus, FO may be useful in preventing CP-induced hepatotoxicity in cancer patients.