The present study aimed to investigate the hepatoprotective effects of the bioflavonoid quercetin (QR) on cisplatin (CP)-induced mitochondrial oxidative stress in the livers of rats, to elucidate the role of mitochondria in CP-induced hepatotoxicity, and its underlying mechanism. Isolated liver mitochondria were incubated with 100 mu g/ml CP and/or 50 mu M QR in vitro. CP treatment triggered a significant increase in membrane lipid peroxidation (LPO) levels, protein carbonyl (PC) contents, and a decrease in reduced glutathione (GSH) and non-protein thiol (NP-SH) levels. In addition, CP caused a marked decline in the activities of enzymatic antioxidants and mitochondrial complexes (I, II, III and V) in liver mitochondria. QR pre-treatment significantly modulated the activities of enzymatic antioxidants and mitochondrial complex enzymes. Furthermore, QR reversed the alterations in LPO and PC levels, and GSH and NP-SH contents in liver mitochondria. The results of the present study suggested that QR supplementation may suppress CP-induced mitochondrial toxicity during chemotherapy, and provides a potential prophylactic and defensive candidate for anticancer agent-induced oxidative stress.