Objective To explore the effect of lncRNA BLACAT1 expression on radiation resistance in nasopharyngeal squamous cell carcinoma. Methods FaDu/RR cells were divided into control group, si-NC group, and si-BLACAT1 group. CCK8 method was used to detect cell viability under 0 Gy, 4 Gy, 8 Gy, and 12 Gy irradiation. Flow cytometry was used to detect cell apoptosis levels under 4 Gy radiation dose. Immunofluorescence and protein immunoblotting were used to detect the expression levels of human microtubule associated protein light chain protein 3I (LC3I), human microtubule associated protein light chain 3II (LC3II), p62, and Beclin1 proteins. Real time fluorescence quantitative PCR (qPCR) was used to detect the expression levels of LC3I, LC3II, p62, and Beclin1 genes. The nude mouse model of human hypopharyngeal squamous carcinoma cell transplantation was constructed with FaDu/RR cells and divided into si-NC group and si-BLACAT1 group. The tumor volume and mass were determined. The protein expression levels of Ki67, VEGF-C and VEGFR-3 were detected by immunohistochemistry. The protein expression levels of ATG5, ATG7 and ATG12 were detected by immunoimprinting.Results The CCK8 experiment results showed that compared to the si-NC group, the activity of FaDu/RR cells in the si-BLACAT1 group was significantly reduced under 4 Gy, 8 Gy, and 12 Gy irradiation (P＜0.05). Flow cytometry analysis of cell apoptosis showed that after 4 Gy radiation dose treatment, the apoptosis level of FaDu/RR cells in the si-BLACAT1 group was significantly increased compared to the si-NC group (P＜0.0001). The results of protein immunoblotting and immunofluorescence experiments showed that, the expression levels of LC3II, p62, and Beclin1 proteins in the si-BLACAT1 group were higher than those in the si-NC group, while the LC3I protein was lower than that in the si-NC group; qPCR experiments showed that the expression level of LC3I gene in the si-NC group was higher than that in the si-BLACAT1 group.LC3II, p62, and Beclin1 genes were higher in the si-BLACAT1 group than in the si-NC group. The results of a nude mouse model of human hypopharyngeal squamous cell carcinoma cell transplantation showed that the tumor weight and volume in the si-BLACAT1 group were significantly lower than those in the si-NC group (all P＜0.0001). In addition, the expression of ki67, VEGF-C, and VEGFR-3 in the tumor tissue of the si-BLACAT1 group was lower than that of the si-NC group, and the autophagy related proteins ATG5, ATG7, and ATG12 in the tumor tissue of the si-BLACAT1 group were higher than those of the si-NC group. Conclusion LncRNA BLACAT1 enhances radiotherapy resistance in hypopharyngeal squamous cell carcinoma by regulating the autophagy pathway in FaDu/RR cells