Objective: To investigate the prognostic value of serum albumin (SA) levels before chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL) after re-ceiving chemotherapy. Methods: This is a retrospective study, and 127 patients with DLBCL including 71 males (55.9%) and 56 females (44.1%) were included. Patients' gender, age, Ann Arbor staging, eastern cooperative oncology group (ECOG) score, treatment options, inter-national prognostic index, response rate, overall sur-vival (OS), and progression-free survival (PFS) were ob-tained for statistical analysis. Results: Univariate analysis showed that SA5_34 g/L, Ann Arbor III-IV, B symptoms, ECOG >= 2, and bone marrow involvement suggest a poor prognosis in patients with DLBCL. Patients with persis-tent SA>34 g/L had significantly longer OS than patients with persistent SA5_34 g/L (P=0.020). Multivariate analy-sis showed that SA5_34 g/L (HR=0.48, 95% CI=0.26-0.90, P=0.022) and R-CHOP-like treatment regimen (HR=0.43, 95% CI=0.24-0.76, P=0.004) are independent factors that could affect the prognosis of patients with DLBCL. Con-clusion: SA can be used as an indicator of prognosis in patients with DLBCL before the first chemotherapy. DLBCL patients with SA5_34 g/L are associated with short OS and poor prognosis, which may potentially provide guidance for the clinician to pay more attention to this population before the first chemotherapy.