Abstract: Objective: To investigate the expressions of S100A4 protein in oral squamous cell carcinoma(OSCC) and its significance.Methods: Expression of S100A4 protein was detected by using immunohistochemistry SP method in 61 patients with OSCC and 20 cases of normal mucosa.Relationship between the expression of S100A4 protein and clinicopathological features was analyzed.Results: The positive expression rate of S100A4 protein was 24.6% in OSCC,but negative expression in NOM.The difference in the positive expression rate of S100A4 protein was statistically significant between the OSCC and NOM(P<0.05).Expression of S100A4 protein in OSCC had positive correlation with lymph node metastasis(P<0.01),and no correlation with histological grading(P>0.05).Conclusions: S100A4 protein is related with invasion and metastasis of OSCC.Expression of S100A4 protein is significantly associated with tumor progression in OSCC,which was one of the valuable markers for predicting biological behavior and trend of metastasis of OSCC.