A local invasion and lymph node metastasis (LNM) of an oral squamous cell carcinoma (OSCC) has a poor prognosis, and involves the degradation of the extracellular matrix mediated by multiple proteolytic enzymes including membrane type I-matrix metalloproteinase (MT1-MMP). This study aimed to determine the role of MT1-MMP in OSCC, to evaluate the immunohistochemical expression of MT1-MMP with regard to the invasiveness and LNM of the OSCC, and to evaluate the major source of MT1-MMP mRNA and its protein using immunohistochemistry and in situ hybridization. MT1-MMP expression was examined in 46 OSCCs via immunohistochemistry and non-radioisotope in situ hybridization. The relationship between MT1-MMP expression and LNM, as well as the histological invasiveness, was statistically analyzed. The results showed that whereas 12 out of the 18 OSCCs (66.7%) with LNM showed moderate to strong MT1-MMP expression, only nine of the 28 OSCCs (32.1%) without LNM expressed MT1-MMP strongly. MT1-MMP expression was significantly higher with regard to LNM (P=0.022). As the invasion grade became stronger (from grade a to grade d), MT1-MMP was significantly more strongly expressed (P=0.033). These results suggest that MT1-MMP is primarily secreted in the OSCC cells and is involved in the invasiveness of the OSCC and LNM. Moreover, MT1-MMP combined with other markers may be used to predict the metastatic potential of an OSCC.