Over-expression of integrin αvβ6 and increased numbers of cancer-associated fibroblasts (CAFs) play an important role in the development and progression of cancers. The aim of this study is to investigate the expression level of integrin αvβ6 and CAF numbers, their correlation with clinicopathologic features and their role in the prognosis of human gastric cancers. The expression levels of integrin αvβ6 and α-SMA in CAFs were analyzed by immunohistochemistry. Their correlation with clinicopathologic features, the relationships and the survival time of patients were also analyzed. The integrin αvβ6 expression levels were analyzed mainly in gastric cancers. The α-SMA expression levels were analyzed mainly in gastric cancers and paraneoplastic tissues. Patients with positive integrin β6 and α-SMA expression have a significantly lower overall survival rate than those with negative integrin β6 and α-SMA expression (P < 0.05). A multivariate analysis using a log-rank test indicated that patients with positive integrin β6 and α-SMA expression and/or a diffuse type of gastric cancer had a significantly poorer overall survival rate than did those with negative integrin β6 expression (P < 0.05). Integrin β6 expression correlated significantly with CAF numbers and served as a valuable prognostic indicator for human gastric cancers.