Abstract: Objective This study used to investigate the association between overexpressed phosphdiesterase 4B (PDE4B) and the prognosis of diffuse large B-cell lymphoma (DLBCL) and evaluate its predictive values. Methods Micro-array data of 320 patients with DLBCL was downloaded from gene expression omnibus (GEO) data set. The statistically significant test of overall survival (OS) between high and normal PDE4B expression level was made by Log-rank test. Univariate (international prognostic index, IPI or PDE4B) and multivariate (IPI+PDE4B) Cox proportional hazards model were constructed and time-dependent receiver operating characteristic curves method was used to analysis the tendency of model's predictive power over time. The overall prediction accuracy of each model was evaluated and compared with the C index. Results The risk of death in DLBCL patients with overexpressed PDE4B was 1.431 times (HR=1.431,95% CI:1.013-2.002, P=0.042) that of normal expression. C index was statistically significant difference (IPI vs. IPI+PDE4B:Z=15.0, P<0.001;PDE4B vs. IPI+PDE4B:Z=53.7, P<0.001) between multivariate and univariate Cox regression model. Conclusions Overexpressed PDE4B is a hazard for DLBCL. Prognostic accuracy of DLBCL may be improved by combining IPI and PDE4B.