Purpose Nasal type extranodal natural killer/T-cell lymphoma (ENKTL) can be associated with hemophagocytic lymphohistiocytosis (NK/T-LAHLH), which is a rare and fatal disease with no effective therapy. We evaluated whether etoposide + dexamethasone-based chemotherapy regimens might be useful for treating NK/T-LAHLH. Methods This retrospective single-center study evaluated clinical data from 37 patients with NK/T-LAHLH who were treated between May 2008 and January 2020. Results Among 363 patients with ENKTL, the cumulative incidence of HLH was 11.9%. Among 43 patients with NK/T-LAHLH, 37 patients received etoposide + dexamethasone-based chemotherapy regimens, with an overall response rate of 45.9% for the HLH. The overall response rate was substantially higher for newly diagnosed NK/T-LAHLH than it was for relapsed or refractory NK/T-LAHLH (66.7% vs. 18.8%). The median overall follow-up time was 4 months, with overall survival rates of 81.1% at 1 month, 62.2% at 2 months, 56.8% at 3 months, and 34.4% at 6 months. Significantly better overall survival (all P< 0.05) was observed for patients with newly diagnosed NK/T-LAHLH (vs. relapsed/refractory disease), stage I/II disease (vs. stage III/IV disease), and nasal disease (vs. non-nasal disease). Patients who responded to the ENKTL treatment also experienced response in their HLH; 8 patients experienced continued complete response for both HLH and ENKTL. Multivariate analysis revealed that a poor prognosis among patients with NK/T-LAHLH was independently related to relapsed/refractory ENKTL and non-nasal disease. Conclusion Although patients with NK/T-LAHLH generally experienced poor outcomes, etoposide + dexamethasone-based chemotherapy regimens were associated with good outcomes among select patients with newly diagnosed or stage I/II NK/T-LAHLH.