Abstract: Objective To investigate the expression of tight junction-associated protein Claudin-5 in gastric adenocarcinoma and its clinical significance. Methods Forty-two specimens of gastric adenocarcinoma from January 2011 to December 2016 in North China University of Technology were collected.The normal gastric mucosa tissue adjacent to the tumor edge>5 cm was used as the control.The expression of Claudin-5 protein was detected by immunohistochemistry.And the TCGA database was used to analyze the expression of Claudin-5 mRNA in gastric adenocarcinoma tissues and normal tissues. Results The positive rate of Claudin-5 expression in gastric adenocarcinoma tissues was significantly lower than that in paracancerous tissues (38.10% vs 80.95%,P<0.05).The positive rate of Claudin-5 expression in well differentiated gastric adenocarcinoma tissues (100%) was significantly higher than that in moderately differentiated expression tissue (28.6%) and poorly differentiated expression tissue (32.3%) (P<0.05,respectively).The positive expression of Claudin-5 in gastric adenocarcinoma tissues had no significant correlation with gender,age,lymph node metastasis,presence of cancerous thrombus,presence of cancer nodules and depth of invasion.In the TCGA database,Claudin-5 mRNA expression in cancer tissues was lower than that in normal tissues. Conclusion Claudin-5 is down-regulated in gastric adenocarcinoma tissues.