Radiation therapy is the mainstay of salvage therapy for nasopharyngeal carcinoma (NPC). However, radiation therapy efficacy is limited by radioresistance that can cause local recurrence and distant metastases. Circular RNAs (circRNAs) have been involved in radioresistant esophageal cancer cells. In this study, we aim to investigate the role of circRNAs in the radioresistant NPC. Human circRNA array was performed in radioresistant and radiosensitive NPC samples to screen the differentially expressed circRNAs. We found that circRNA_000543 expression was upregulated in NPC tissues compared adjacent tissues, and was higher in radioresistant samples than in radiosensitive NPC samples. NPC patients with high circRNA_000543 expression displayed poorer overall survival compared with the patients with low circRNA_000543. Further investigations demonstrated that circRNA_000543 knockdown sensitized NPC cells by targeting miR-9/platelet-derived growth factor receptor B (PDGFRB) axis. CircRNA_000543 may be a potential therapeutic target for radioresistant NPC.Keywords: Circular RNAs; Nasopharyngeal carcinoma; Platelet-derived growth factor receptor B; Radiation therapy; miR-9.