Long non-coding RNAs (lncRNAs) have played crucial roles in various cancers, including nasopharyngeal carcinoma (NPC). In our study, we focused on the biological function and clinical significance of lncRNA LINC00460 in NPC. It was indicated that LINC00460 was markedly increased in NPC tissues and cells compared to their corresponding controls. Silencing LINC00460 was able to suppress NPC cell growth in vitro while overexpressing LINC00460 reversed this process. Moreover, in vivo tumor xenografts were established using CNE-1/SUNE-1 cells to detect the function of LINC00460 in NSCLC tumorigenesis. Rescue assay was performed to further confirm that LINC00460 contributed to the progression of NPC through regulating miR-149-5p/IL6 signal pathway. In conclusion, we have uncovered that LINC00460 could be regarded as a novel prognostic biomarker and therapeutic target in NPC diagnosis and treatment. •LINC00460 is up-regulated in human primary NPC tissues;•Expression of IL6 is up-regulated in primary human NPC and negatively expressed related to miR-149-5p;•miR-149-5p inhibits the tumorigenic potential of NPC cells by down-regulating oncogenic IL6 gene;•LINC00460's oncogenic functions are partially through reverse regulation of miR-149-5p, and then activation of IL6.