OBJECTIVE: To clarify the relationship between the expression of NEDD9 in gastric cancer and the invasion and metastasis of the tumor. STUDY DESIGN: The postoperative pathological samples of 40 patients with gastric cancer receiving surgical resection from January 2014 to August 2016 in our hospital were selected as subjects. All gastric cancer tissues were confirmed as gastric adenocarcinoma by histopathological examination, and the patients did not receive any treatment before surgery. Meanwhile, paracancerous tissues < 3 cm away from the foci were collected. HE staining showed that 24 cases had moderate-severe atypical hyperplasia; of those, 20 were taken for experimental studies. In addition, 40 cases of normal gastric mucosal tissues confirmed by gastroscopy and pathological examination were selected as controls. All samples were subjected to immunohistochemical assay, in situ hybridization, RT-PCR, and Western blot. RESULTS: The positive expression rates of NEDD9 protein in normal gastric mucosal tissue, paracancerous atypical hyperplastic tissue, and gastric cancer tissue were 7.5%, 20%, and 92.5%, respectively. The NEDD9 mRNA expressions in normal gastric mucosal tissue, paracancerous atypical hyperplastic tissue, and gastric cancer tissue also followed an ascending order. CONCLUSION: The overexpression of NEDD9 was closely related to the onset and progression of gastric cancer, and increase in its expression may be an early warning event. © Science Printers and Publishers, Inc.