Objective?To understand the possible role of signal transducer and activator of transcription 1 (STAT1) and interferon-γ (IFN-γ) in the generation of local lesions of oral lichen planus (OLP). Methods?Formalin-fixed, paraffin-embedded tissues of 10 cases of normal oral epithelium and 48 cases of OLP were investigated for STAT1 and IFN-γ proteins by using immunohistochemistry SABC method. The correlation between the expression of STAT1 and IFN-γ proteins and the clinical and pathological characteristics in OLP were statistically analyzed. Results ① STAT1 and IFN-γ were over expressed compared with healthy oral mucosa (P<0.05). ② The percentage of STAT1 over-expression in OLP with positive IFN-γ staining was significantly higher than that in OLP with negative IFN-γ staining (χ2=5.042,?P<0.05). A positive correlation between the over-expression of STAT1 and IFN-γ was seen in OLP (r=0.324, P<0.05). ③ The percentage of over-expression of STAT1 in OLP with disease course less than 6 months was higher than that in OLP with disease course more than 6 months (χ2=5.077, P<0.05), and a positive correlation was observed between the over-expression of IFN-γ and the liquefaction of base cells in local lesions of OLP (r=-0.388, P<0.05). Conclusion?The over-expression of STAT1 and IFN-γ may participate in the generation of local pathological damnification of OLP at the early stage.