Abstract: Objective: To investigate the effect of p53 protein accumulation and p53 gene mutation in the pathogenesis of glioma and to study the role of MDM2, p53 and P16 protein in glioma formation and progression, as well as the correlations between them. Methods: The LSAB immunohistochemical staining method and non-isotopic PCR-SSCP techniques were used to detect the expression of the proteins MDM2, p53 and P16 and, the p53 gene mutation in 48 cases with human encephalic gliomas. Results: The positive expression rate of MDM2, p53 and the negative rate P16 protein was 22.9%, 41.7% and 60.4%, respectively. The expression of the p53 and the negative rate of P16 protein in the gliomas with high potential malignancy were significantly higher than that in those with lowpotential malignancy. Moreover, the co-expression of Mdm2 and p53 protein was confirmed in only 1 of the 48 cases. PCR-SSCP results showed that in 17 cases abnormal bands were detected in one of the 5-8 exons of p53 gene. The mutations were detected in16 of the 20 cases with positive expression of p53 and the negative expression was found in another case. The concordance rate of immunohistochemistry and PCR-SSCP was 89.6%. In 7 cases (41.2%), the mutations located in exon 5, 1 (5.9%)was in exon 6, 4 (23.5%) in exon 7 and 5 (29.4%) in exon 8, respectively. p53 gene mutation and the level of MDM2, p53 and P16 protein were not related to age, gender of patients, tumor location and size. Conclusion: The mutation of p53 and deletion of P16 may play an important role in the tumorigenesis of glioma and it is significantly associated with the differentiation of the tumor.