Cisplatin mediated nephrotoxicity has been continuously reported and recognized as a major obstacle for cisplatinbased chemotherapy. The present study aimed to demonstrate the potential use of silymarin, an extract from the seed of Silybum marianum L., as a combination therapy with cisplatin. Previous studies indicated that cisplatin-mediated toxicity was primarily caused by cellular oxidative stress. This study found that pretreatment with silymarin significantly attenuated oxidative stress induced by cisplatin in human renal epithelial cells (HK2-cells) and protected against cisplatin-mediated apoptosis. Moreover, the present study demonstrated that silymarin could attenuate hydrogen peroxide and hydroxyl radical generated by cisplatin while having minimal effect on superoxide anion level. In summary, these observation showed significant impact of silymarin in the inhibition of cisplatin-mediated renal cell death in vitro and could be beneficial for the development of this compound as a combination therapy in patients before receiving cisplatin.