BACKGROUND: This study directs to evaluate the efficacy and safety of intensity-modulated radiotherapy (IMRT) alone versus IMRT plus chemotherapy in intermediate-risk NPC (stage II and TNM). METHODS: A total of 124 patients with stage II and TNM NPC were pair-matched (1:1 ratio) to form two groups: an IMRT-alone group and an IMRT/chemotherapy group. Survival outcomes (overall survival [OS], disease-free survival [DFS], locoregional relapse-free survival [LRRFS], distant metastasis-free survival [DMFS]) and treatment-related grade 3-4 acute toxicity events were compared between the groups. RESULTS: Survival outcomes for patients with stage II and TNM NPC were quiet comparable between patients treated with IMRT alone versus patients treated with IMRT/chemotherapy: 5-year OS was 91.9% vs. 90.3%, respectively (P = 0.727); DFS was 87.1% vs. 88.7%, respectively (P = 0.821); LRFFS was 96.8% vs. 95.2%, respectively (P = 0.646), and DMFS was 91.9% vs. 91.5%, respectively (P = 0.955). Grade 3 acute toxicities were significantly higher with IMRT/chemotherapy than with IMRT alone: mucositis, 15% vs. 5% (P = 0.004); leukopenia/neutropenia, 8% vs. 1% (P <  0.015); and nausea/vomiting, 22% vs. 3% (P <  0.001). CONCLUSION: For intermediate-risk (stage II and TNM) NPC patients, the addition of chemotherapy to IMRT does not appear to provide any survival benefit. Moreover, grade 3 acute toxicities are also more common in patients receiving IMRT plus chemotherapy.