Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of lymphoma, with different clinical manifestation and prognosis. The International Prognostic Index (IPI), an index designed during the prerituximab era for aggressive lymphoma, showed variable values in the prediction of patient clinical outcomes. The aim of this study was to analyze the prognostic value and causes of pretreatment liver injury in 363 de novo DLBCL patients in our institution. Pretreatment liver impairment, commonly detected in lymphoma patients, showed significant association with poor outcomes and increased serum inflammatory cytokines in DLBCL patients but had no relation to hepatitis B virus replication nor lymphomatous hepatic infiltration. Multivariate analysis revealed that liver dysfunction, advanced Ann Arbor stage, and elevated lactate dehydrogenase (LDH) were independent adverse prognostic factors of both PFS and OS. Accordingly, a new liver-IPI prognostic model was designed by adding liver injury as an important factor in determining IPI score. Based on Kaplan-Meier curves for PFS and OS, the liver-IPI showed better stratification in DLBCL patients than either the IPI or the revised IPI in survival prediction.