Aim Aralia elata (Miq.) Seem is a medicinal plant with a variety of biological activities.Several trierpene saponins extracted from the leaves of Aralia elata (Miq.) Seem possess potent cytotoxic activity, but the mechanisms remain unclear.Methods In the present study, we examined the antitumor activity of total saponins of Aralia elata (Miq.) Seem leaves (TSAESL) using both in vitro and in vivo experiments, and investigated the underlying molecular mechanisms.Results Briefly, TSAESL significantly inhibited the proliferation of five human cancer cell lines and induced apoptosis of MCF7 cells in a concentrationdependent manner.TSAESL also increased the expression level of active caspase3 and cleaved PARP.In addition, TSAESL dramatically activated the phosphorylation of ERK1/2, p38 and JNK in a concentrationdependent manner.Treatment with the ERK1/2 inhibitor U0126, p38 inhibitor SB203580, or JNK inhibitor SP600125 prior to TSAESL exposure markedly attenuated TSAESLinduced phosphorylation of ERK1/2 and p38.In mice bearing MCF7 xenograft, TSAESL markedly inhibited tumor growth without significantly affecting spleen coefficient and hematological parameters.Conclusion These results strongly suggest that TSAESL has antitumor effect via activating the MAPKmediated signaling pathways.