Abstract: Objective To investigate the effect and mechanism of sesamin on antiproliferation and apoptosis induction of human lung adenocarcinoma cell line A-549 in vitro, and provide a theory basis for traditional medicine treatment in antineoplastic therapy. Methods Human lung adenocarcinoma cell line A549 was cultivated in vitro. Then the effect of antiproliferation and cytotoxicity of sesamin on human lung adenocarcinoma cell line A549 was analyzed by MTT; Morphological changes were observed by inverted microscope and HE staining; Flow cytometry was used to investigate the expression of Bcl-2 and Bax; The apoptosis rate was determined by AnnexinV/PI staining; The changes of apoptosis protein kinase such as Caspase-3, Caspase-8, Caspase-9 were detected by immunohistochemistry. Results MTT assay showed that sesamin had signifi cant inhibition on the growth of A549 cell line in dose- and time-dependent manner; It was observed by inverted microscope the volume of the cell A549 was decreased and got round, nuclear condensed chromatin, the junction between cell was loosed, adherence ability was decreased. A typical cell morphology changes such as the cytoplasm dehydrated and concentrated was showed by HE staining and enhanced feosin staining; Immunohistochemical assay showed that the expression of Caspase-3, 8, 9 was increased compared with those in control group, it had a signifi cantly difference (P<0.05); Flow cytometry showed a cell apoptosis peak after treated by 40 μg/ml sesamin for 48 h, and the number of cell was increased in S phase and decreased in G0/G1 phase, and most cell stay in S phase. The expression of Bcl-2 was decreased, while the expression of Bax was increased. Conclusion Sesamin can signifi eantly inhibit the growth of A549 cells and the effect is dose-dependent and time-dependent. Sesamin could arrest the A549 cells in the S phase. Sesamin induced apoptosis via two main pathways: the mitochondrial pathway and the death receptor-mediated pathway. Sesamin has a signifi cant effect on anti-tumor. It will be hopefully exploited as a new anti-tumor or tonic.