<b><i>Background/Aims: </i></b>Periplocin is extracted from the traditional herbal medicine cortex periplocae, which has been reported to suppress the growth of cancer cells. However, little is known about its effect on gastric cancer cells. <b><i>Methods: </i></b>Gastric cancer cells were treated with periplocin, and cell viability was assessed using MTS assay. Flow cytometry and TUNEL staining were performed to evaluate apoptosis, and protein expression was examined by western blotting. Microarray analysis was used to screen for changes in related genes. <b><i>Results: </i></b>We found that periplocin had an inhibitory effect on gastric cancer cell viability in a dose-dependent manner. Periplocin inhibited cell viability via the ERK1/2-EGR1 pathway to induce apoptosis. Periplocin also inhibited the growth of tumor xenografts and induced apoptosis <i>in vivo</i>. <b><i>Conclusion: </i></b>Our results show that periplocin inhibits the proliferation of gastric cancer cells and induces apoptosis <i>in vitro</i> and <i>in vivo</i>, indicating its potential to be used as an antitumor drug
