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BACKGROUND Our preliminary sequencing analysis revealed increased expression levels of circNUP98 in nasopharyngeal carcinoma (NPC). This study was therefore carried out to explore the role of circNUP98 in NPC. METHODS The present study enrolled 56 patients with NPC, 44 patients with cervical lymphadenitis (CL), 50 patients with nose bleeding (NB), 50 patients with chronic sinusitis (CS), 50 patients with lymph node tuberculosis (LNT), and 50 healthy controls (Control). Plasma samples were obtained from all patients and the controls. In addition, NPC and paired non-tumor tissue samples were collected from the 56 NPC patients. Expression of circNUP98 in both tissue and plasma samples was determined by RT-qPCR. The 56 NPC patients were followed up for 5 years to analyze the associations between plasma expression of circNUP98 and the survival of patients. The diagnostic value of circNUP98 for NPC was analyzed through ROC curve analysis. RESULTS The plasma expression levels of circNUP98 were only increased in NPC, but not in CL, NB, CS and LNT groups compared to that in the Control group. In addition, increased expression levels of circNUP98 was observed in NPC tissues compared to that in non-tumor tissues. Plasma circNUP98 was closely correlated with circNUP98 in NPC tissues, but not circNUP98 in non-tumor tissues. With plasma circNUP98 as a biomarker, NPC patients were separated from CL, NB, CS, LNT and the Control groups. Plasma expression of circNUP98 was found to be positively correlated with the poor survival of patients. Moreover, plasma circNUP98 was only closely associated with tumor metastasis, but not tumor size. CONCLUSION The expression of circNUP98 in plasma may be used to diagnose NPC and predict patients' survival.