The endothelial cell protein C receptor (EPCR) has been reported to be involved in the development of several human cancers. However, the role of EPCR in gastric cancer progression has not been clarified. In this study, we show for the first time that EPCR is related to gastric cancer. Our results indicate that EPCR is highly expressed in clinical gastric cancer tissue. Knockdown of EPCR by small interference RNA suppressed the proliferation and migration of MGC803 gastric cancer cells dominantly. Blocking antibodies to protease-activated receptor-1(PAR1) also suppressed the proliferation and migration of MGC803 cells. Knockdown EPCR and blocking PAR1 inhibit activation of extracellular signaling-regulated kinases 1 and 2 (ERK1/2). Taken together, these results indicate that EPCR contributes to the proliferation and migration of MGC803 gastric cancer cells by activating ERK1/2, and this effect of EPCR may be dependent on PAR1. Therefore, EPCR may be act as a novel therapeutic target for inhibiting cell growth in gastric cancer.