Background: Serum amyloid A (SAA) has been associated with the development and prognosis of cancer. The purpose of this study was to evaluate the predictive value of integration of pretreatment SAA–EBV DNA (S‐D) grade and comparison with the TNM staging system in patients with nasopharyngeal carcinoma (NPC). The S‐D grade was calculated based on the cut‐off values of serum SAA and EBV DNA copy numbers which were determined by receiver operating characteristic (ROC) curves. We evaluated the prognostic value of pretreatment SAA, EBV DNA and S‐D grade on overall survival (OS) of NPC patients. We also evaluated the predictive power of S‐D grade with TNM staging system using 4 indices: concordance statistics (C‐index), time‐dependent ROC (ROCt) curve, net reclassification index (NRI) and integrated discrimination improvement (IDI).Results: A total of 304 NPC patients were enrolled in this study. Multivariate analysis showed that TNM stage (P = 0.007), SAA (P = 0.013), and EBV DNA (P = 0.033) were independent prognostic factors in NPC. The S‐D grade was divided into S‐D grade 1, S‐D grade 2, and S‐D grade 3, which had more predictive accuracy for OS than TNM staging according to all 4 indices.Conclusions: We found that the S‐D grade could be used as a new tool to predict the OS in NPC patients.