Abstract: Objective To investigate the effect of elevated serum amyloid A(SAA) on the prognosis of patients with locally advanced nasopharyngeal carcinoma(NPC). Methods The clinical and follow-up data of 315 patients with staged Ⅲ-ⅣA/B NPC was analyzed. Fifty-three patients with elevated SAA were enrolled in the SAA-H group. According to sex, age, KPS score, T stage, N stage and clinical stage, 106 normal SAA patients(SAA-N) were obtained by the propensity matching method. Kaplan-Meier method was used to calculate survival rate and Cox regression model was used to analyze prognostic factors. The primary endpoints was overall survival(OS), and the secondary endpoints were no loco-regional relapse-free survival(LRRFS) and distant metastasis-free survival(DMFS). Results Of the 315 patients with local advanced NPC, the 4-years OS of SAA-H group was 66.0% vs. 82.1% compared to SAA-N group(P=0.007); the 4-years LRRFS of SAA-H group was 86.8% vs. 90.1% compared to SAA-N group(P=0.385); the 4-years DMFS of SAA-H group was 58.5% vs 77.5% compared to SAA-N group(P=0.001). Among the 159 patients enrolled by the propensity-matching method, the prognosis was significantly worse in the SAA-H group than in the SAA-N group, 4-years OS: 66.0% vs. 80.2%(P=0.044); 4-years LRFSS 86.8% vs. 92.5%(P=0.198); 4-years DMFS 58.5% vs. 74.5%(P=0.023). Cox regression model showed that elevated SAA was an adverse prognostic factor for OS and DMFS. Conclusion The elevated SAA is a prognostic factor for death and metastasis in patients with locally advanced NPC. Pre-treatment SAA levels combined with TNM staging can be used to classify patients and to guide the choice of clinical treatment intensity.