The treatment for patients with stage IVc nasopharyngeal carcinoma (NPC) at diagnosis was still controversial. In this study, we tried to build a prognostic score model and optimize the treatment for the patients. The prognostic model was based on the primary cohort involving 289 patients from 2002 to 2011 and the validation involving another 156 patients from 2012 to 2015.The prognostic model was built based on the hazard ratios of significant prognostic factors for overall survival (OS). By multivariate analysis, factors associated with poor OS were Karnofsky performance score ≤70, liver metastases, multiple-organ metastases, ≥2 metastatic lesions, lactate dehydrogenase >245 IU/I and poor response to chemotherapy (all P < 0.01). Based on these prognostic factors, patients were divided into the low-risk (0-2 points), intermediate-risk (3-6 points) and high-risk (≥7 points) groups. Five-year OS rates for the low-, intermediate- and high-risk groups were 49.3%, 9.7% and 0.0%, respectively (P < 0.01). Furthermore, loco-regional radiotherapy was associated with significantly better OS in low- and intermediate-risk patients, but not in high-risk patients. These results demonstrated that the prognostic score model based on six negative factors can effectively predict OS in patients with stage IVc NPC at diagnosis. Loco-regional radiotherapy may be beneficial for low- and intermediate-risk patients, but not for high-risk patients.