Abstract: Objective: To investigate the clinical efficacy and safety of ruxolitinib phosphate and etoposide combined with cisplatin, dexamethasone, gemcitabine, and pegaspargase (RuE-DDGP) as an initial induction regimen for the treatment of natural killer/T-cell lymphoma-associated hemophagocytic syndrome (NK/T-LAHS). Methods: The clinical data for 11 patients with NK/T-LAHS treated with the RuE-DDGP regimen in The First Affiliated Hospital of Zhengzhou University from January 2021 to June 2022 were retrospectively analyzed for treatment efficacy, adverse effects, and prognosis. Results: Among the 11 patients, there were nine males and two females, with a median age of 30 (20–75) years. After 2 weeks of treatment, all 11 patients achieved partial remission (PR), with an overall remission rate (ORR) of 100%. After 4 weeks of treatment, 10 patients achieved PR and one was not evaluated due to death. The median overall survival （mOS) time was 3 (0.7–15.5) months, and the median progression-free survival (mPFS) time was 3 (0.7–15.5) months. No treatment-related serious adverse events were observed during the follow-up period. Conclusions: The RuE-DDGP treatment regimen is safe and effective for patients with NK/T-LAHS during initial induction therapy.