The aim of this study was to determine the clinical significances of p53 and p-glycoprotein (P-gp) expression on outcome predictors for patients with DLBC. We assessed the immunohistochemical expression of p53 and P-gp using formalin-fixed, paraffin-embedded specimens in 108 patients diagnosed with de novo DLBC. A high expression of p53 was found in 53.7% of the patients. No expression of P-gp was demonstrated in any of the specimens. There were no significant differences in the complete remission (CR) rate (P = 0.79), overall survival (OS) (P = 0.73), or disease-free survival (DFS) (P = 31) between the p53-positive and p53-negative groups. The final model from multivariate analysis that revealed poor performance status was significantly associated with CR (P < 0.001) and OS (P < 0.001). Moreover, the advanced stage was a significant predictor of DFS (P = 0.03). This study demonstrated no impact of the expression of p53 on either response or survival rates.