Natural killer (NK)/T-cell lymphoma-associated hemophagocytic lymphohistiocytosis (NK/T-LAHLH) is a rare and life-threatening disorder. Its clinical characteristics and appropriate treatment options are unclear. This study aimed to investigate the clinical characteristics and treatment options for this disease. We retrospectively analyzed the clinical data of 84 patients with NK/T-cell lymphoma and compared the characteristics, treatment, and survival between patients with and without HLH. Patients in the NK/T-LAHLH group were more likely to be younger age and have hepatosplenomegaly, B symptoms, neutropenia, anemia, thrombocytopenia, elevated lactate dehydrogenase levels, reduced serum albumin levels, bone marrow involvement, Ann Arbor stage III/IV, and International Prognostic Index score ≥ 3. After multivariate analysis, it was found that elevated lactate dehydrogenase and Ann Arbor stage III/IV were risk factors for HLH in patients with NK/T-cell lymphoma. After 2 weeks of therapy, 78.6% (11/14) patients who received the L-DEP/DEP regimen achieved an overall response rate of HLH, which was higher than that in 42.9% (9/21) patients who received the VP-16 + dexamethasone-based regimen. NK/T-LAHLH patients had poorer survival than non-HLH-NK/TCL patients. For NK/T-LAHLH, the L-DEP/DEP regimen may have a better response rate than the VP-16 + dexamethasone-based regimens.© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.