PURPOSE: We investigated the safety and efficacy profile of intensity-modulated radiation therapy (IMRT) followed by gemcitabine, dexamethasone, cisplatin (GDP), plus chidamide in the first-line setting for intermediate- and high-risk early-stage extranodal natural killer/T-cell lymphoma, nasal type (ENKTCL). METHODS: This was an open-label, randomized phase 2 trial performed at 2 centers in China. Patients were eligible if they were newly-diagnosed with intermediate- and high-risk early-stage ENKTCL with at least one risk factor based on a nomogram-revised risk index: >60 years old, elevated serum lactate dehydrogenase, invasion of the primary tumor, stage II or Eastern Cooperative Oncology Group performance status >1 or stage II disease. Patients were treated with IMRT followed by GDP, with or without chidamide, in the first-line setting. Two-year progression-free survival (PFS) comprised the primary endpoint. Toxicities, the 2-year overall survival (OS), and the response rate comprised the secondary endpoints. RESULTS: Eligible patients (N = 74) were enrolled between May 2015 and December 2019. Among them, 37 patients were treated with IMRT + GDP + chidamide (chidamide group), whereas 37 cases were treated with IMRT + GDP (control group). Follow-up comprised a median of 43.4 months (range, 1.0-74.6 months). The objective response rate was 86.5% in the chidamide group and 78.4% in the control group (P = .359) at the end of treatment completion. The 2 year OS and PFS rates were 89.2% and 75.2% in the chidamide group versus 83.8% (P = .388) and 70.2% (P = .821) in the control group. The main adverse events were hematological toxicities and mucositis, with similar rates in the 2 groups (P > .05). CONCLUSIONS: The addition of chidamide to IMRT + GDP as first-line treatment achieved similar treatment outcomes and tolerable toxicities compared with IMRT + GDP in patients with intermediate- and high-risk early-stage ENKTCL.