Chimeric antigen receptor (CAR) T-cell therapy is an effective treatment for diffuse large B-cell lymphoma (DLBCL). However, it may activate the systemic immune system of the patient, resulting in cytokine release syndrome (CRS). Emapalumab is a human monoclonal antibody targeting interferon-γ, inhibiting its interaction with cell surface receptors and the subsequent activation of inflammatory pathways. The present report describes the cases of 2 patients with relapsed DLBCL treated with CAR T-cell therapy, in which the severe CRS associated with CAR T-cell therapy was attenuated without compromising antitumor efficacy after receiving emapalumab. Further prospective clinical trials are warranted to determine the role of emapalumab in CAR T-cell therapy.