Objective To investigate the expression and clinical significance of FOXP3 in oral squamous cell carcinoma（OSCC）and adjacent tissues. Methods EnVision immunohistochemistry method was used to detect the expression level of FOXP3 protein in 156 cases of oral squamous cell carcinoma and 96 cases of adjacent tissue microarray. The relationships of FOXP3 expressions with clinicopathological characteristics and prognosis were analyzed，and the results were compared with TCGA database sample analysis results. Results The high expression rates of FOXP3 in the OSCC tissues and adjacent tissues were 57.69% and 20.83%，respectively and the difference the in expression rate was statistically significant between the groups（P < 0.000 1），which was consistent with the results from the TCGA database analysis. Its expression was significantly correlated with T staging（P = 0.003）and TNM staging（P = 0.020）. By Kaplan⁃Meier and COX regression analysis，the related factors affecting the prognosis were high expression of FOXP3（P = 0.012），T stage（P = 0.031），and TNM stage（P = 0.032）. By COX multiple factors analysis ，the independent factor affecting the prognosis was high expression of FOXP3（P = 0.009）. Conclusion The protein of FOXP3 is highly expressed in OSCC tissues and related to the poor prognosis of OSCC patients.