Abstract： Objective To examine Prion protein (PrP) expression and its clinical significance in oral mucosa,oral leukoplakia,oral squamous cell carcinoma(OSCC) and its subgroups.Methods Expression of PrP in OSCC,oral leukoplakia and mucosa specimen was detected by immunohistochemistry.The association between the expression and gender,TNM clinical stages,pathological grades was evaluated.Results The positive expression rate of PrP in normal,oral leukoplakia and OSCC tissues was 15 ％ (3/20),42 ％ (11/26) and 95 ％ (80/84),respectively.There was a significant difference between the expression of PrP in leukoplakia and in high,moderately and poorly differentiated OSCC (P ＜ 0.05).The positive expression rate was increased with the declining of pathological differentiation (P ＜ 0.05).There was no significant difference in PrP expression among lymph node metastasis and gender.PrP expression of stages I and Ⅱ was up-regulated with the decreased differentiation (P ＜ 0.05).There was no significant difference in PrP expression between stage Ⅲ and Ⅳ (P ＞ 0.05).Between stages Ⅰ + Ⅱ and Ⅲ + Ⅳ in the overa Ⅱ expression of PrP,there was a significant difference (P ＜ 0.05).Conclusions The high expression of PrP in OSCC and the progressive expression from leukoplakia to OSCC was closely related to the carcinogenesis of OSCC,pathologic stage and clinical TNM stage.