Sophocarpine is one of the major ingredients of Sophorae flavescentis which could inhibits many kinds of cancers. However, the effect of sophocarpine on gastric cancer (GC) and the mechanism involved remain unknown. The present study aims to explore the effects of the sophocarpine on the proliferation and apoptosis of GC cells and elucidates the relevant molecular mechanisms. After treatment with sophocarpine, GC cells were evaluated on their proliferation, autophagy, cell cycle progress and apoptosis. The protein levels of LC3-I, LC3-II, Beclin, p62, PTEN, PI3K, p53, Bax, Bcl-2, AKT and p-AKT were detected by western blot. Sophocarpine inhibited the proliferation of GC cells both in vitro and in vivo dose-dependently. Sophocarpine not only caused cell apoptosis and cell cycle arrest in G0/G1 phase but also induced cell autophagy. Moreover, sophocarpine dose-dependently suppressed PI3K/AKT signaling pathway and activated apoptosis in gastric cancer cells. Thus, sophocarpine significantly inhibited the growth of GC cells through multiple mechanisms such as induction of autophagy, activation of cell apoptosis and down-regulation of cell survival signaling pathway.