Long non-coding RNAs (lncRNAs) are aberrantly expressed and have important functions in pathological processes. The present study investigated the lncRNA profiles and the effects of curcumin (Cur) on the radiosensitivity of nasopharyngeal carcinoma (NPC) cells. The lncRNA and mRNA profiles of each cell group were described by microarray analysis. Numerous differentially expressed genes were observed by microarrays in three cell groups. Cur significantly reversed the IR-induced lncRNA and mRNA expression signatures, shown by clustering analysis. Moreover, 116 of these IR-induced and Cur-reversed differentially expressed lncRNAs were obtained. Six lncRNAs (AF086415, AK095147, RP1-179N16.3, MUDENG, AK056098 and AK294004) were confirmed by qPCR. Furthermore, functional studies showed that lncRNA AK294004 exhibited a negative effect on cyclin D1 (CCND1), indicating that CCND1 might be a direct target of AK294004. IR-induced differentially expressed lncRNAs were reversed during Cur-enhanced radiosensitization in NPC cells, suggesting that lncRNAs have important functions in IR-induced radioresistance. Thus, Cur could serve as a good radiosensitizer.