Objective:To investigate the effect of LINC00261 on the radiosensitivity of nasopharyngeal carcinoma and tumor formation and its underlying mechanism in nude mice.Methods:qRT-PCR was used to detect the relative expression levels of miR-620 and LINC00261 in radiosensitive and radioresistant nasopharyngeal carcinoma tissues. After the 6-10B and HNE-3 cells were irradiated with 0, 2, 4, 6, and 8 Gy 60Coγ-ray, the relative expression levels of miR-620 and LINC00261 were measured by qRT-PCR. After over-expression or silencing of LINC00261 and inhibition of miR-620 expression, the cells were irradiated with 4 Gy 60Coγ-ray. Clone formation assay was performed to detect the radiosensitivity of nasopharyngeal carcinoma cells. Flow cytometry was used to detect cell apoptosis. Western blot was utilized to detect the expression levels of Cleaved caspase-3 and Cleaved caspase-9 proteins. Luciferase reporter assay was adopted to analyze the targeting relationship between LINC00261 and miR-620. The changes in tumor formation were observed in tumor-bearing nude mice. Results:Compared with the radiosensitive tissues, the expression of LINC00261 was significantly down-regulated, whereas that of miR-620 was significantly up-regulated in radioresistant tissues (both P<0.05). After different doses of irradiation, the expression of LINC00261 was significantly down-regulated, whereas that of miR-620 was significantly up-regulated in 6-10B and HNE-3 cells (both P<0.05). After overexpression of LINC00261 and interference with miR-620 expression, the expression levels of Cleaved caspase-3 and Cleaved caspase-9 were significantly up-regulated (both P<0.05), the cell apoptosis rate was remarkably increased ( P<0.05) and the cell survival fraction was significantly enhanced in 6-10B and HNE-3 cells ( P<0.05). LINC00261 targetedly regulated the expression of miR-620. Overexpression of miR-620 could attenuate the radiosensitization and pro-apoptotic effects of LINC00261 overexpression on nasopharyngeal carcinoma cells. LINC00261 overexpression could significantly reduce the tumor formation weight of nasopharyngeal carcinoma in nude mice ( P<0.05). Conclusion:Overexpression of LINC00261 can increase the radiosensitivity of nasopharyngeal carcinoma cells probably by targeted regulation of miR-620 expression.