Objective: To investigate the correlation between P53 and ATRX protein expression in IDH1 mutant and wild type glioblastoma (GBM) and its biological significance. Methods: A total of 62 cases of tissue samples were collected from the Department of Pathology of Guangdong Tongjiang Hospital (including 12 cases of IDH-1 mutant GBM, 50 cases of IDH1 wild type GBM detected by immunohistochemistry). The expression of P53 and ATRX protein in these two different genotyping GBMs were detected and their relationship with prognosis were analyzed. Results: The expression rates of P53 protein in IDH1 mutant and wild type GBM were 75.00% (9/12) and 30.00% (15/50) respectively, and the expression rates of ATRX protein were 16.67% (2/12) and 94.00% (47/50), respectively. The expression of P53 and ATRX protein in the two genotypes of IDH1 was statistically significant (P<0.01). P53 and ATRX were negatively correlated (r=−0.404, P<0.01). Cox multiple regression analysis showed that IDH1 genotype, age and sex were the risk factors of GBM survival (P<0.01). Conclusion: Most of the IDH1 wild-type GBM patients lack the P53 gene and the ATRX gene mutation. IDH1 wild-type GBM is a significant factor affecting the survival time of GBM, which can be used as one of the important indexes to judge the prognosis of adult GBM patients.