Abstract: Diffuse large B-cell lymphoma (DLBCL) is highly heterogeneous and the most common type of invasive non-Hodgkin lymphoma. Therefore, the prognostic evaluation of DLBCL is particularly important for patients before and during the treatment. With the rapid development of molecular biology techniques and immunotherapy, the traditional prognostic assessment methods have been greatly challenged. Considerable attention has been paid toward the accurate prognostic evaluation of patients using multiple methods. Various serum biomarkers have been recently implicated in the prognostic evaluation of DLBCL. Serum biomarkers are non-invasive, convenient, and highly sensitive, and the tests for serum biomarkers are more easily acceptable to patients. Therefore, the role of serum biomarkers in the comprehensive evaluation of DLBCL prognosis cannot be ignored. This article reviews the research progress on serum biomarkers for the prognostic evaluation of DLBCL.