Evodiamine-induced apoptosis has been shown to have anticancer activity by eradication of some carcinoma cell lines. This study was designed to evaluate the effects of evodiamine on the viability of human gastric cancer SGC-7901 cells and to define the cell death pathway. Flow cytometry detection showed that 1.5 μM evodiamine significantly induced SGC-7901 cell apoptosis in a time-dependent manner. This apoptosis was partially inhibited by the pancaspase inhibitor carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoro-methylketone, which suggests that evodiamine-induced apoptosis in SGC-7901 cells is partially caspase independent. Further, the total content of sphingomyelin was decreased and expression of acid sphingomyelinase (aSMase) and neutral SMase genes in the SGC-7901cells was upregulated. Protein expression of aSMase, which was exposed to evodiamine, was shown to be increased by western blot analysis and could have been responsible for inducing caspase-independent apoptosis. Our results indicate that evodiamine stimulates upregulation of aSMase expression and hydrolysis of sphingomyelin into ceramide, which might be one of the mechanisms by which apoptosis occurs in SGC-7901 cells.