The purpose of this study was to investigate the clinical significance of FOXP1 and p65 expression in diffuse large B-cell lymphoma (DLBCL). Immunohistochemistry was performed to determine the expression of FOXP1 and p65 protein in 92 DLBCL tissues and analyze their correlations with clinicopathological features or prognosis of patients. The survival was assessed by the Kaplan-Meier method and proportional hazards model. Results showed that positive FOXP1 expression was detected in 68 (73.9%) cases and positive p65 expression was detected in 56 (60.9%) cases. There were 46 (50.0%) co-expression of FOXP1 and p65 protein in all cases, a positive correlation between the expression of FOXP1 and p65 was noted (r=0.234, p=0.025). The status of FOXP1 was correlated with patient's age, worse performance status score, higher lactate dehydrogenase levels and International Prognostic Index (IPI) factor score. The status of p65 was correlated with patient's age, B symptom and higher IPI factor scores. Both FOXP1 and p65 protein expression were associated with the non-GCB phenotype (p=0.001 or 0.000). The Kaplan-Meier curves showed that both FOXP1 and p65 expression were associated with poor survival of patients. Meanwhile, FOXP1+/p65+ subgroup had the worst PFS (p=0.012) and OS (p=0.030), whereas the FOXP1-/p65- subgroup had the best prognosis. Thus, immunohistochemical assessment of both FOXP1 and p65 status in DLBCL tissues may be a valuable approach for predicting the survival of DLBCL patients.