Abstract: Objective To investigate the role of microsatellite instability(MSI) in gastric carcinoma and its relationship with CLIC4 expression. Methods The MSI of D1S234, D1S199, D1S507 in 40 cases of gastric carcinoma and paired normal control tissues were detected by PCR, native polyacrylamide gel electrophoresis and silver staining; and the expression of CLIC4 in these 40 cases and another 55 cases were detected by immunohistochemical analysis at the same time. Results The MSI positive rate of D1S234, D1S199 and D1S507 were 25% (10/40), 27.5% (11/40) and 5% (2/40), respectively. There was no statistically significant difference among various histological types (P > 0.05). In 40 cases of gastric carcinoma tissues, the positive rate of CLIC4 in tumor epithelial cells was 25%(10/40), and in tumor stroma was 67.5%(27/40), the negative and positive rates in both tumor epithelial cells and stroma were 15%(6/40) and 12.5%(5/40), respectively. Spearman rank correlation analysis showed that D1S199 MSI was positively correlated with CLIC4 positive rate in tumor epithelial cells (r=0.137, P=0.042), and D1S507 MSI was negatively correlated with CLIC4 positive rate in tumor stroma (r=-4.22, P=0.009). In 95 cases of gastric cancer specimens, the positive rate of CLIC4 in tumor stroma was 72.6%(69/95), in tumor epithelial cells was 51.6%(49/95), and the positive rate in both was 24.2%(23/95). The positive rate of CLIC4 in tumor stroma was significantly higher than that in tumor epithelial cells (χ²=8.945, P=0.003), tumor stroma positive cases were mainly poorly-differentiated and mucous adenocarcinoma, and tumor epithelial positive cases were mainly well-moderately differentiated adenocarcinoma. CLIC4 interstitial positive rate was increased in poorly-differentiated cases. Conclusion MSI of D1S199 and D1S507 are intimately related with the occurrence of gastric carcinoma; CLIC4 may be associated with tumor interstitial fibrosis in gastric cancer, and promote the evolution of gastric carcinoma.