Abstract: Objective To investigate the expression and clinicopathological significance of FXYD3(Mat-8)protein in gastric adenocarcinoma. Methods SP immunohistochemical method was to used to detect the expression of FXYD3 in paraffin-embedded sections from 29 cases of normal gastric mucous tissue and 51 cases of gastric adenocarcinoma. Results The positive expression rate of FXYD3 protein in gastric adenocarcinoma was 66.67%(34/51), which was higher than that 27.59%(8/29) in normal gastric mucous tissue. The statistically difference was significant (P<0.05). FXYD3 protein expression was not obviously correlated with patient 's gender, age and tumor size,general types,histological classification as well as lymph node metastasis (P>0.05). Conclusion Up-regulation of the FXYD3 protein expression may be an early event of genesis in gastric adenocarcinoma, and it may not be obviously correlated with invasion and metastasis of gastric adenocarcinoma.