Objective To investigate the inhibitory and apoptotic effect and possible mechanism of ursolic acid(UA) on the proliferation of human non-small cell lung cancer A549 cells. Methods The effect of UA on the proliferation of A549 cells was measured by MTT method. Hoechst 33258 fluorescent dying was used to observe UA induced morphological changes. The cell cycle was observed with flow cytometry. The activated protein level of Caspase-3 and NF-κB was detected by Western blot. Results UA strongly inhibitied the growth of A549 cells in a dose-and time-dependent manner. Cell cycle analysis revealed that A549 cells treated by UA for 24h and 48h were blocked predominantly in G_0/G_1 phase (P 0.05 ). The morphological changes of apoptosis, such as nuclear fragmentation or condensed particles were identified after incubation by UA. The expression of activated Caspase-3 increased in a time-dependent manner, simultaneously, UA time-dependently decreased NF-κB protein. Conclusion UA has the effects of inhibition to A549 cell proliferation and induction of cell apoptosis. NF-κB plays an important role in regulating cell proliferation and apoptosis in lung cancer. UA can inhibit NF-κB activity and elevate the expression of Caspase-3, which is related to an increased cell apoptosis.