Objective: To assess the prognostic and predictive significance of p53 protein expression in low O6-methylguanine- DNA methyltransferase (MGMT) expressing glioblastoma multiform (GBM) treated with combined therapy. Methods: The authors reviewed the clinical outcomes of 46 low MGMT expressing GBM patients who had undergone surgery, conventional local radiotherapy and temozolomide chemotherapy. Correlation between p53 expression level and clinical outcomes were analysed with univariate and multivariate Cox model. Results: Patients with low p53 expression had a significantly improved progression free survival (PFS) (p=0.015) and overall survival (OS) (p=0.047) compared to those with high expression. On both univariate and multivariate analyses, low p53 expression persisted as a significant independent favorable prognostic factor for PFS (p=0.017). Pre-operative Karnofsky performance status score (p=0.029), tumor resection extent (p=0.045) and p53 expression level (p=0.038) were significant independent prognostic factors for OS. Conclusion: In these low MGMT expressing GBM patients with combined treatment, low p53 expression was a significant independent favorable prognostic factor for both PFS and OS. In addition to MGMT, p53 may be another stratification variable in the future therapeutic trials.