Objective: To evaluate the therapeutic effect and reactions of hyperfractionated radiotherapy combined with concurrent chemotherapy for nasopharyngeal carcinoma (NPC) in stages III and IV. Methods: Sixty previously untreated NPC patients were randomly assigned to hyperfractionated radiotherapy plus chemotherapy (experimental group) and hyperfractionated radiotherapy (control group). Irradiation dose to the NPC foci were: experimental group 1.2 Gy/f, 2f/d, to a total dose of 75.5 Gy; for neck nodes: 79 Gy to patients with positive nodes. PFL was used in chemotherapy regimen: PDD: 60 mg·m -2, d1; 5-FU 750 mg·m-2, d2~4, Lv 100 mg·m-2, d2~4, q4w. Results: The experimental group had a higher complete regression rate of tumor and a higher 1, 3 and 5 year survival rate than the control group (P < 0.05), but it had more serious irradiation reactions than the control group (P < 0.05). Conclusion: Hyperfractionated radiotherapy plus chemotherapy has better therapeutic effects with tolerable reactions. Therefore, combination of hyperfractionated radiotherapy with chemotherapy regimen for NPC patients seems justified.