OBJECTIVE To study the expression and its relationship of murine double minute 2 (MDM2), P53 protein in oral leukoplakia and squamous cell carcinoma. METHODS Immunohistochemical assay was used to detect the expression of MDM2 and P53 proteins in 15 normal oral epithelium tissues, 24 cases of oral leukoplakias and 41 cases of oral squamous cell carcinomas. RESULTS There were no positive expression of MDM2 and P53 in normal mucosa. With significantly difference compared with the normal group (P < 0.05), the positive rates of MDM2 and P53 were 58.3%, 75.6% and 37.5%, 68.3% in oral leukoplakia and squamous cell carcinoma. MDM2-positive rate had no significant difference (P > 0.05), while P53-positive rate was significant difference (P < 0.05) compared with oral leukoplakia and oral squamous cell carcinoma. Two kinds of indicators for further correlation analysis showed that MDM2 and P53 protein showed a positive correlation relationship both in oral leukoplakia (P = 0.018) and oral squamous cell carcinoma (P = 0.000). CONCLUSION The expression of MDM2 in oral leukoplakia and oral squamous cell carcinoma suggests that this gene may play a significant role in the process of carcinogenesis of oral squamous cell carcinoma. The correlation of MDM2 and P53 expression indicates that both of them may play a synergistic role in the process of carcinogenesis of oral squamous cell carcinoma.