Serum microRNAs (miRNAs) have been reported as novel biomarkers for various diseases. But circulating biomarkers for predicting the radiosensitivity of nasopharyngeal carcinoma (NPC) have not been used in clinical practice. To screen out of differently expressed serum miRNAs from NPC patients with different radiosensitivity may be helpful for its individual therapy. NPC patients with different radiosensitivity were enrolled according to the inclusion and exclusion criteria. RNA was isolated from serum of these NPC patients before treatment. We investigated the differential miRNA expression profiles using microarray test (GSE139164), and the candidate miRNAs were validated by reverse transcription-quantitative real time polymerase chain reaction (RT-qPCR) experiments. Receiver operating characteristic (ROC) analysis has been applied to estimate the diagnostic value. In this study, 37 serum-specific miRNAs were screened out from 12 NPC patients with different radiosensitivity by microarray test. Furthermore, RT-qPCR analysis confirmed that hsa-miR-1281 and hsa-miR-6732-3p were significantly downregulated in the serum of radioresistant NPC patients (P < 0.05), which was consistent with the results of microarray test. ROC curves demonstrated that the AUC for hsa-miR-1281 was 0.750 (95% CI: 0.574-0.926, SE 87.5%, SP 57.1%). While the AUC for hsa-miR-6732-3p was 0.696 (95% CI: 0.507-0.886, SE 56.3%, SP 78.6%). These results suggested that hsa-miR-1281 and hsa-miR-6732-3p in serum might serve as potential biomarkers for predicting the radiosensitivity of NPC.