Gamma-glutamyl transpeptidase (GGT) which plays an important role in tumor initiation, invasion, drug resistance is strongly associated with poor prognosis in patients with cancers. This study was designed to estimate whether pretreatment serum GGT could predict the clinical outcome of nasopharyngeal carcinoma (NPC) patients. An optimal cutoff value was identified as 23 U/L for GGT. Univariate analysis and multivariate analysis demonstrated that elevated GGT was correlated with shorter local recurrence-free survival (LRFS) (HR, 4.163; 95% CI, 1.690-10.251; p=0.023), progression-free survival (PFS) (HR, 3.119; 95% CI, 1.955-4.976; p=0.031) and overall survival (OS) (HR, 2.811; 95% CI, 1.614-4.896; p=0.007). We retrospectively analyzed data from 374 patients with NPC. Kaplan-Meier method was used to calculate and compare the prognosis. The Cox proportional hazards model was applied to carry out univariate and multivariate analyses. Pretreatment GGT can be a novel and independent prognostic biomarker for patients with NPC.