Objective：This study aims to investigate the expression of CD109 in oral squamous cell carcinoma（OSCC）and its influence on clinical characteristics and prognosis. Methods：The expression of CD109 mRNA and protein in OSCC tissues were detected by real-time quantitative PCR and immunohistochemistry respectively. The relationships between CD109 expression and clinical characteristics and prognosis were analyzed according to clinicopathological data. Results：The mRNA and protein expression levels of CD109 in OSCC tissues were significantly higher than those in paracancerous oral tissues. CD109 expression was associated with lymph node metastasis（P=0.019），distant metastasis（P=0.007）and cancer stage according to American Joint Committee（P=0.031）. Multivariate analysis confirmed that CD109 expression was an independent prognostic factor for OSCC patients（P < 0.001）.OSCC patients with high CD109 expression had a poor overall survival compared with patients with low or none CD109 expression（P=0.004）. Conclusion：CD109 is an independent risk factor affecting the prognosis of OSCC patients，and may be an important marker to predict the prognosis of OSCC.