The impacts of weight loss on prognosis in nasopharyngeal carcinoma (NPC) remain unclear. The present study was therefore undertaken to investigate the association between critical weight loss and long-term survival in NPC patients. The eligible 2399 NPC patients were reviewed. Weight change was categorized into critical weight loss (CWL) and non-critical weight loss (Non-CWL). The associations of CWL with long-term survival were analyzed by Cox regression in the entire patient and two subsets. Propensity score matching was performed to reduce the effects of confounding factors. CWL was defined as body weight loss of ≥4.6 %. Compared with patients without CWL, patients with CWL had significantly lower 5-year OS (72.4 vs. 79.3 %, P < 0.001), FFS (71.1 vs. 78.4 %, P <0.001), and LR-FFS (78.1 vs. 84.8 %, P <0.001), respectively. After adjustment for potential confounders, CWL remained an independence prognostic factor for OS (HR = 1.352; 95 % CI 1.160–1.576; P < 0.001), FFS (HR = 3.275; 95 % CI 1.101–9.740; P = 0.033), and LR-FFS (HR = 6.620; 95 % CI 2.990–14.658; P < 0.001), respectively. Furthermore, subgroup analysis in the cohort of patients received concurrent chemoradiotherapy or radiotherapy alone confirmed the results in the entire patient even after the propensity-score matching. In IMRT cohort, CWL was also significantly associated with a lower OS (P = 0.04) and FFS (P = 0.04). CWL has a significant and independent impact on long-term survival in nasopharyngeal carcinoma patients.