Background: The prognosis of nasal type advanced-stage or relapsed extranodal NK/T cell lymphoma (ENKTL) is poor even with intensive multi-agent chemotherapy. It is therefore critical to develop more effective treatment strategies to improve outcomes and prognosis of ENKTL patients. Methods: We conducted a multi-center, prospective study to evaluate the efficacy and safety of a new treatment strategy: induction chemotherapy with gemcitabine, L-asparaginase or PEG-asparaginase, ifosfamide, dexamethasone and etoposide (GLIDE) followed by upfront autologous hematopoietic stem cell transplantation (ASCT) conditioning with either carmustine, etoposide, cytarabine, and melphalan (BEAM) or chidamide, cladribine, gemcitabine, and busulfan (ChiCGB). Findings: A total of 64 eligible patients were enrolled. After a maximum of 6 cycles of GLIDE, 43 patients (70·5%) achieved complete response, including 31 (50·8%) who achieved complete response after 2 cycles. With median follow-up of 23.8 months, estimated 5-year progression-free survival and overall survival of the whole cohort was 54·0% and 68.9% respectively. Among 50 chemo-sensitive patients (patients in complete or partial remission) , 27 underwent upfront ASCT, and they showed a significantly higher rate of 5-year progression-free survival than chemosensitive patients who did not receive upfront ASCT (78·8% vs. 36·0%, p=0·0004) as well as a significantly higher rate of 5-year overall survival (87·2% vs. 55·4%, p=0·0035). Interpretation: GLIDE chemotherapy showed a high efficacy in disease control for the patients with advance-staged or relapsed ENTKL, and in whom achieved partial or complete response, GLIDE followed by upfront ASCT may be a more effective treatment strategy than GLIDE alone. Trial Registration Information: The study was registered at the Chinese Clinical Trial Registry (Chictr.org.cn, Chicrt-TNC-10000782). Funding Statement: This work was supported by a grant from Science and Technology Fund of Sichuan Province, China, NO.18ZDYF2063. Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: This study was approved by the Ethics Committee of West China Hospital, Sichuan University. Written informed consent was obtained from all patients.