Background Epithelial mesenchymal transition (EMT) participates in the radioresistance of cancer cells. In this study, we evaluated whether interleukin-6 (IL-6) regulates EMT and subsequent radioresistance in nasopharyngeal carcinoma (NPC) cells. Methods Western blot was used to analyze the expression of proteins. Immunofluorescent assay was performed to detect the position and content of specific proteins. Colony formation assay was applied to measure the proliferation ability of NPC cells. Flow cytometry was adopted to measure cell apoptosis. Results NPC cells seen with typical morphological transition and unique proteins change of EMT when exposed to irradiation. IL-6 and its downstream signal molecules elevated in irradiated cells. Blocking IL-6 with anti-IL-6 receptor antibody hampered EMT and radioresistance. Cell radiosensitivity and apoptosis rates in irradiated NPC cells declined significantly upon IL-6 stimulation. Conclusion Irradiation could induce EMT and activate IL-6 signaling in NPC cell lines. Blocking IL-6 was able to inhibit EMT and cellular radioresistance.