We investigated whether the expression levels of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), and plasminogen activator inhibitor-1 (PAI-1) correlate with clinicopathological features of oral squamous cell carcinoma (SCC). We immunohistochemically examined the expression levels of uPA, uPAR, and PAI-1 in 160 biopsy specimens of oral SCC. Positive stainings for uPA, uPAR, and PAI-1 were observed mainly in SCC cells, and their intensity and number of positive cells were related to lymph node involvement (p < 0.001, p < 0.001, and p < 0.001, respectively). The expression levels of uPA and uPAR were also related to the pattern of invasion (p < 0.05 and p < 0.001, respectively), while both were associated with tumor size (p < 0.05). Moreover, a poor survival rate was related to the expression of uPAR (p < 0.01) and PAI-1 (p < 0.05). These findings suggest that the uPA system may regulate the invasion and metastasis of oral SCC cells.