Matrix metalloproteinases (MMPs) MMP-2 and MMP-9 can degrade type IV collagen of extracellular matrix and basal membranes. Claudin-4 is a member of a large family of transmembrane proteins, claudins, essential in the formation and maintenance of tight junctions. Claudin-4 has been shown to activate MMP-2, indicating that claudin-mediated increased cancer cell invasion might be mediated through the activation of MMP proteins. To explore the roles of MMP-2, MMP-9 and claudin-4 in gastric cancer, we selected 88 cases and then analyzed the expression of these proteins using immunohistochemistry. We found that all of MMP-2, MMP-9 and claudin-4 expressions were significantly higher in intestinal-type than in diffuse-type gastric cancer. On further analysis, testing the relationship between MMP-2 and MMP-9 expression with claudin-4 expression, claudin-4 expression was significantly associated with MMP-9 expression, but not with MMP-2 expression. The results showed that MMP-2, MMP-9 and claudin-4 expression may be phenotypic features, distinguishing intestinal-type and diffuse-type gastric cancer. Possibly, claudin-4 played a role in determining MMP-9 activity which favored intestinal-type gastric cancer to distal metastasis.