Objective To investigate the expression of IFITM3 in gastric cancer and its effect on malignant biological behavior of gastric cancer cells. Methods The expression of IFITM3 in gastric cancer was analyzed by database and the correlation between IFITM3 and overall survival rate of gastric cancer patients was analyzed. Si-ifitm3 was transfected into GASTRIC cancer cells SGC-7901, and cell proliferation, apoptosis and migration were analyzed by CCK-8 assay, flow cytometry and wound healing assay. The phosphorylation of P38-MAPK and the expression of EMT-related proteins (e-cadherin, Snail and Vimentin) were detected by Western blot. Results IFITM3 was highly expressed in gastric cancer and negatively correlated with the overall survival rate of gastric cancer patients. Transfection of SI-IFITM3 in SGC-7901 cells could effectively knock down the expression of IFITM3. Knocking down IFITM3 can significantly inhibit cell proliferation and migration, induce cell apoptosis, and also reduce the phosphorylation of P38-MAPK and the expression of EMT-related proteins. Conclusion Knockdown IFITM3 can inhibit EMT of gastric cancer cells by reducing phosphorylation of P38-MAPK protein, thus slowing down cell proliferation and migration, and inducing cell apoptosis.