Purpose: To investigate the capacity of aqueous Pseuderanthemum paltiferum leaf extracts (PPA) to induce apoptosis in A549 human lung cancer cells and the possible mechanisms of action. Methods: Human lung cancer A549 cells were cultured in the presence of PPA (0-1000 µg/mL). Cell viability was assessed by MTT assay while morphological alterations in the cells were observed by Hoechst 33342/PI double staining. Intracellular reactive oxygen species (ROS) levels and subsequent changes of mitochondrial membrane potential were also investigated. Involvement of caspase-3 activation in the apoptotic pathway was determined. Results: PPA inhibited the growth of A549 cells in a concentration-and time-dependent manner. Major phenotypic apoptotic cell death was evidenced in microscopic images. Furthermore, treatment of A549 cells with PPA resulted in a significant increase in the production of ROS accompanied by attenuation of mitochondrial membrane potential, thus inducing the activation of caspase-3 activity (p < 0.05). Conclusion: PPA exerts anti-cancer activity by suppression of cell viability and induction of ROSmediated mitochondrial dependent apoptosis in A549 cells, and may be a potential candidate for the development of a therapeutic agent for lung cancer.