The aim of this study was to investigate the relationship between psychosocial distress and quality of life (QOL) in patients with nasopharyngeal carcinoma (NPC) after radiotherapy. Fifty-three patients with an initial diagnosis of NPC were enrolled in this study. The psychological Distress Thermometer (DT) and Functional Assessment of Cancer Therapy-Head & Neck (FACT-H&N) were conducted before and after radiotherapy in NPC patients. We compared the differences in psychological distress and QOL before and after radiotherapy and analyzed the correlation between psychological distress and QOL after radiotherapy. The performance on the DT was 6.60 ± 1.42 and 2.81 ± 1.43 before and after chemotherapy, respectively, with a significant difference between the time points (t = -13.73, P < 0.01). The performance on the FACT-H&N was 68.30 ± 6.14 and 39.84 ± 6.14 before and after chemotherapy, respectively, with a significant difference between the time points (t = -19.9, P< 0.01). There was a significant negative correlation between the DT score and the FACT-H&N score (r = -3.64, P< 0.01). Patients with NPC experience different degrees of psychological distress, an important factor that affects quality of life, after radiotherapy.