BACKGROUND Radiation resistance poses a major clinical challenge in treatment of nasopharyngeal carcinoma (NPC). Studies have shown that the abnormal expression of microRNAs (miRNAs) is associated with radiosensitivity, however, the mechanisms have not been fully elucidated. The aim of this study, therefore, was to investigate whether ectopic expression of miR-124 is correlated with radiosensitivity in NPC. METHODS In this study, the expression level of miR-124 was evaluated in NPC cell lines and patient specimens using quantitative reverse transcription-PCR (Real-time qPCR). Cell radiosensitivity was determined by colony formation assay. Target prediction algorithms and luciferase assay were used to confirm the target of miR-124. Tumor xenograft model was performed to understand the functions of miR-124 in vivo. RESULTS We found that miR-124 was down-regulated in both NPC specimens and NPC cell lines. Ectopic expression of miR-124 increased radiosensitivity of NPC cells. In vivo assays extended the significance of these results, showing that miR-124 overexpression decreased cell resistance to radiation treatment in tumor xenografts. Furthermore, we identified PDCD6 as a novel direct target of miR-124. Functional studies showed that knockdown PDCD6 enhanced cell radosensitivity to irradiation, and PDCD6 could rescue the effect caused by overexpression of miR-124, indicating that PDCD6 is a functional target of miR-124. CONCLUSIONS MiR-124 enhances cell radiosensitivity by targeting PDCD6, miR-124/PDCD6 axis may facilitate the development of novel targeted therapies for NPC.