Background: Curcumin, a component of turmeric (Curcuma longa), is known to inhibit proliferation of tumor cells and induce apoptosis in cancer cells by regulating cancer-related genes. Statin, a potent inhibitor of HMG-CoA is known to induce cell cycle arrest and stimulate apoptotic cell death in various human cancer cell lines. However, the precise molecular anti-cancer mechanisms of these agents are not yet elucidated in lung cancer cells. Results: A549 cell was treated with curcumin and simvastatin for 24, 48 or 72 h. The agents inhibited the growth of the cell in a concentration dependent manner, especially the synergistic inhibition of cell proliferation with simvastatin (1 uM) and curcumin (20 uM) on all indicated times. The agents directly increased intracellular reactive oxygen species (ROS) level by flow cytometric analysis. ROS were significantly increased after treatment with curcumin and simvastatin up to 24 h (p＜0.05) and then were decreased. Curcumin also significantly promoted the expression of apoptosis related genes such as p53 and p21 after 12 h exposure of 20 uM curcumin. Curcumin or curcumin and simvastatin decreased the mRNA expression of cyclin D1. Conclusions: Our data indicates that combination of curcumin and simvastatin has synergistic anti-proliferative effects and increases intracellular ROS level and expression of p53 in lung cancer cell. These results suggest that a ROS-mediated apoptosis pathway played an important role in response to curcumin or simvastatin involves increasing the expression of p53.