Objective To study the expression and significance of EGFR, PDCD4, TGF-β1, Smad3, Smad7 in oral normal mucosa, oral simple hyperplasia, oral epithelial dysplasia and oral squamous cell carcinomas(OSCC). Methods Serum levels of EGFR, PDCD4 were measeured with ELISA in Chinese hamster during the oral mucosa carcinogenesis; The expressions of TGF-β1, Smad3, Smad7 in oral normal mucosa, oral simple hyperplasia, oral epithelial dysplasia and OSCC tissues were examined by immunohistochemistry. Results In the process of oral carcinogenesis,the expression level of EGFR increased significantly,while the expression of PDCD4 was decreased, the negatively correlation was evident between expression of these two proteins in ED and SCC. The expression of TGF-β1, Smad7 was higher in OSCC than in oral normal mucosa, oral simple hyperplasia, oral epithelial dysplasia(P < 0.05), while the expression of Smad3 was decreased. Further analysis showed the expression of TGF-β1 was correlated with the expression of Smad7. Conclusions The expressions of EGFR, PDCD4, TGF-β1, Smad3, Smad7 are closely related with the biological behaviors of oral squamous cell cancinoma.This experiment provides a theoretical basis for the study of oral squamous cell carcinomas mechanism research. So it has important significance for the development and prognosis of oral squamous carcinomaare.