Maspin, a member of the serpin family of protease inhibitors, is known to have tumor-suppressor functions. However, the association between its expression level and survival has not been demonstrated in human cancer. Using the immunohistochemical technique to examine the expression levels of maspin in 44 cases of oral squamous cell carcinoma (SCC), we found that 66% of the cases expressed low to intermediate levels of maspin and 34% of the cases expressed high levels of maspin. We further examined maspin protein expression in a series of six SCC cell lines from the head and neck, and found that all but one expressed low or no maspin protein. We also compared the clinicopathological features of the oral SCC cases with the maspin expression level, and found that high maspin expression was associated with the absence of lymph node metastasis. More importantly, we showed that higher maspin expression was significantly associated with better rates of overall survival, suggesting that high maspin expression may be a favorable prognostic marker for oral SCC.