Beyond lipid-lowering effect, statins, the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase competitively inhibitors, have recently attracted wide concern on their anticarcinogenic properties in various cancer cells. However, the molecular mechanisms by which statins inhibit cancer cell proliferation remain unclear. In this study, we investigated the effect of simvastatin on cells proliferation and oxidative stress in the A549 lung cancer cells and the mechanisms underlying. MTT assay revealed that simvastatin inhibited the proliferation of A549 cells in a concentration- and time-dependent manner. Treatment with 50 microM simvastatin for 48 h significantly increased reactive oxygen species (ROS) production and malondialdehyde (MDA), a lipid peroxidation production, and augmented the activity of total superoxide dismutase (SOD) and manganese SOD (SOD2). Moreover, western blotting analysis showed that simvastatin effectively up-regulated the SOD2 relative protein level. These findings suggested that simvastatin could inhibit the proliferation of A549 lung cells through oxidative stress and up-regulation of SOD2.