Objective:To study the expression of Stat3,Bcl-2 and cyclinD1 in process of malignant change of oral premalignant lesions. Methods: Expression of Stat3 and cyclinD1 were detected in normal oral epithelia,simple hyperplasia epithelia,dysplasia epithelia and oral squamous cell carcinoma(OSCC) by immunohistochemical assay. Results: From normal mucosa,hyperplasia epithelia,dysplasia epithelia to OSCC,the value of IOD increased stepwise. There were statistical significances of Stat3 expression between every two groups in all groups except for between normal mucosa and hyperplasia epithelia groups,as well as expressions of Bcl-2 and cyclinD1. The expression of Stat3 was linear positively correlated to that of Bcl-2 and cyclinD1. No relationship was found between Bcl-2 and cyclinD1. Conclusion: The relationships among Stat3,Bcl-2 and cyclinD1 indicate that more than one genes participate in the process of malignant change of oral premalignant lesions.