Protein tyrosine phosphatase nonreceptor type 12 (PTPN12) has been recognized as a tumor suppressor gene that may inhibit tumor growth. However, PTPN12 expression in oral squamous carcinoma (OSCC) has not been studied. We showed reduced expression of PTPN12 in OSCC tissues. Decreased PTPN12 expression was significantly associated with clinical stage of the disease (P < 0.01). Moreover, reduction in PTPN12 correlated with the overactivation of STAT3. PTPRD negatively related to STAT3 phosphorylation (R = -0.535). Low expression of PTPN12 and high level of phosphorylation of STAT3 correlated with poor prognosis. Overexpression of PTPN12 inhibited proliferation and migration in OSCC cells. PTPN12 was associated with STAT3 and induced STAT3 dephosphorylation. Moreover, our results suggested that PTPN12 might function through binding and dephosphorylation of STAT3. Therefore, PTPN12 is a potential marker for prognosis of OSCC.