Purpose: To investigate the anti-proliferative effect of pomolic acid on lung cancer cells (A549), and the underlying mechanism. Methods: The viability of pomolic acid-treated A549 cells was determined by MTT and colony formation assays. Cell colony formation was monitored with acridine orange/ethidium bromide (AO/EB) staining. Protein expressions of Bax and Bcl-2 were assayed by western blotting. Results: Pomolic acid suppressed the growth of A549 cells, with an half-maximal inhibitory concentration of (IC50) of 10 mu M (p < 0.05). However, the IC50 of pomolic acid for normal BEAS-2B cells was 80 mu M. Pomolic acid also decreased colony formation of A549 cells. At 20 mu M, the percentage of A549 colonies decreased to 14 % of control. The dose-dependent cytotoxicity of pomolic acid against A549 cells was mediated via induction of apoptosis and oxidative stress. Pomolic acid treatment enhanced the expression of Bax and decreased the expression of Bcl-2 in A549 cells. Moreover, pomolic acid inhibited the migration and invasion in A549 cells in a dose-dependent manner (p < 0.05). Conclusion: These results indicate the potent anticancer effect of pomolic acid against human lung cancer cells. Thus, pomolic acid has promising potential as a lead molecule for the development of chemotherapy.