Objective : To determine whether oxidants are formed as part of the cisplatin-induced apoptotic process, intracellular markers of oxidative stress were examined. Methods : Apoptotic death of HeLa cells by cisplatin was confirmed by flow cytometry. Results : The pre-treatment with glutathione (GSH) significantly attenuated cisplatin-induced apoptosis through the reduction of reactive oxygen species (ROS) accumulation and diminished caspases-3 and 9 protease activity. Furthermore, z-VAD-fink, an inhibitor of pan-caspase, effectively inhibited the activation of caspases and prevented apoptosis by cisplatin, although cisplatin-induced ROS generation was not attenuated. Conclusion : These data indicate that ROS may play a role as an upstream mediator of caspases. Taken together, our results suggest that oxidative stress mediates cisplatin-induced apoptosis in HeLa cells.