Background: As the chemotherapeutic resistance and postoperative relapse rates of gastric cancer rise year by year, searching for novel chemoprevention compounds has become fairly imminent. 2-amino-N-{4-[5-(2-phenanthrenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-phenyl} acetamide (OSU-03012), a derivative of anti-inflammatory drug celecoxib, has recently been shown to have anti-tumor effects. But its roles and underling mechanisms in gastric cancer is rather unknown. Methods: In this study, we show for the first time that OSU-03012 inhibits the growth and potently induces the apoptosis of gastric cancer cells in vitro in a time- and dose-dependent manner. Results: We demonstrate that OSU-03012 induces cell death through endoplasmic reticulum stress (ERS) mediated up-regulation of PTEN, sequentially followed by the suppression of Akt-STAT3 axis, the activation of the mitochondrial membrane protein Bim, mitochondrial damage and finally the release of the caspase family proteases. Conclusions: Our data provide evidences to support OSU-03012 as a potential therapeutic agent for gastric cancer, which may facilitate further preclinical development of anti-tumor drugs.