Our data showed that: (1) TSP50 was significantly up-regulated in most of the gastric cancer cell lines, and contributed to their proliferation and invasion; (2) TSP50 was negatively related with E-Cadherin expression in gastric cancer tissues as well as lymph node metastasis, and combination of TSP50 and E-Cadherin improved the prediction for prognosis and lymph node metastasis; (3) overexpression of TSP50 induced EMT through activating NF-κB signaling pathway to promote gastric cancer metastasis. This evidence concerns the gene PRSS50 and gastric cancer.