Objective:To detect the expression of chicken ovalbumin upstream promoter transcription factor Ⅱ(COUP-TFⅡ) protein in human gastric cancer(GC) tissues,and investigate the potential molecular mechanism of COUP-TFⅡ involved in the development and advancement of GC and its clinical significance. Methods:Paired tumorous and adjacent non-tumorous human gastric tissues were obtained from 66 patients with GC who underwent surgical resection. The expressions of COUP-TFⅡ and MMP-2 protein were detected using immunohistochemistry. The relationship between COUP-TFⅡ and the clinicopathologic factors as well as the correlation of COUP-TFⅡ and MMP-2 were analyzed. Results:COUP-TFⅡ proteins were positively expressed in 65.2%(43/66) and 19.7%(13/66) of GC tissues and paired non-GC tissues,respectively. The expression of COUP-TFⅡ was significantly correlated with the depth of invasion,differentiated grade,lymph node metastasis and tumor-node-metastatsis (TNM) stage (P < 0.05). However,the expression of COUP-TFⅡ was not correlated with the gender,age and volume of GC tissues. Patients with positive COUP-TFⅡ expression had lower mean survival time than those with negative COUP-TFⅡ expression (26.8 ± 2.6 months vs 36.4 ± 3.0 months, χ2 = 4.118,P = 0.042). MMP-2 proteins were positively expressed in 78.8% (52/66) and 34.8% (23/66) of GC tissues and paired non-GC tissues,respectively. Moreover,a positive correlation was found between COUP-TFⅡ and MMP-2 expression in GC tissues. Conclusion:COUP-TFⅡ protein has significant value in determining invasion and metastasis of gastric cancer and assessing prognosis in patients with gastric cancer,and MMP-2 may be involved in the above regulation progress.