ObjectiveHepatitis B virus (HBV) infection is associated with the incidence and prognosis of diffuse large B-cell lymphoma (DLBCL), and previous studies differ in terms of clinical characteristics and prognostic factors. In this study, we explored the clinical features and prognostic characteristics of real-world DLBCL patients infected with HBV.MethodsPatients with pathologically diagnosed primary DLBCL at West China Hospital of Sichuan University were enrolled. Patients with follicular lymphoma-transformed DLBCL, primary central nervous system DLBCL, and hepatitis C virus, hepatitis E virus, human immunodeficiency virus, or syphilis infections were excluded. Ultimately, a total of 941 patients were included in this study. All patients included in the study underwent HBV serum marker testing before treatment. The demographic features, clinical characteristics and treatments of patients with different HBV infection states were collected and analyzed comprehensively to identify prognostic factors for OS and PFS.ResultsStatistical analysis of the data revealed that hepatitis B surface antigen positive (HBsAg +) DLBCL patients were younger and more likely to present with advanced disease, germinal center B cell-like subtype, B symptoms and splenic involvement. There were no significant differences in OS or PFS among patients with different HBV infection statuses (χ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\upchi$$\\end{document}2 = 0.139, P = 0.933; χ2 = 0.787, P = 0.675); R-CHOP/R-CHOP-like regimens improved prognosis in HBsAg + DLBCL patients (OS: χ2 = 7.679, P = 0.006; PFS: χ2 = 9.042, P = 0.003); antiviral prophylaxis for HBsAg + DLBCL patients improved OS and PFS (HR: 0.336, P = 0.012, 95% CI [0.143, 0.788]; HR: 0.397, P = 0.032, 95% CI [0.171, 0.925]), with tenofovir treatment being particularly effective (χ2 = 4.644, P = 0.031; χ2 = 4.554, P = 0.033).ConclusionsHBsAg + DLBCL patients have unique clinical characteristics, and the use of CD20 monoclonal antibody based regimens significantly improves the outcome and prognosis of patients with HBsAg + DLBCL. Anti-HBV therapy, especially tenofovir, improves the prognosis of DLBCL patients with HBV presenting infection. Timely and sustained antiviral prophylaxis should be the standard strategy for treating DLBCL patients with HBV infection to optimize the efficacy of chemotherapy and immunotherapy.