Introduction:Thrombocytosis has been identified as an unfavorable prognostic factor in several types of cancer. This study aimed to evaluate the prognostic value of pretreatment platelet count in association with the TNM staging system and therapeutic regimens in patients with nasopharyngeal carcinoma (NPC). Methods:A total of 2,626 patients with NPC were retrospectively analyzed. Platelet count>300 × 109/L was defined as thrombocytosis. Matched-pair analysis was performed between patients receiving chemoradiotherapy and radiotherapy. Results:Multivariate analysis showed that platelet count was an independent unfavorable prognostic factor for overal survival (OS) [hazard ratio (HR)=1.810, 95%confidence interval (CI)=1.531–2.140, P<0.001] and distant metastasis–free survival (DMFS) (HR=1.873, 95%CI=1.475–2.379, P<0.001) in the entire patient cohort. Further subgroup analysis revealed that increased platelet count was an independent unfavorable prognostic factor for OS and DMFS in patients with NPC stratified by early and advanced T category, N category, or TNM classification (al P≤0.001). Receiver operating characteristic (ROC) curves verified that the predictive value of TNM classification for OS was improved when combined with pretreatment platelet count (P=0.030). Matched-pair analysis showed that chemoradiotherapy significantly improved OS only in advanced-stage NPC with thrombocytosis (HR=0.416, 95%CI=0.226–0.765, P=0.005). Conclusions:Pretreatment platelet count, when combined with TNM classification, is a useful indicator for metastasis and survival in patients with NPC. It may improve the predictive value of the TNM classification and help to identify patients likely to benefit from more aggressive therapeutic regimens.