In conclusion, our study elucidates that NSUN2 promotes NPC radioresistance by negatively regulating the TP53/RAD51 axis, and the NSUN2 inhibitor GSK-F1 functions as a radiosensitizer in NPC by disrupting the NSUN2/TP53/RAD51 signaling pathway, thereby providing a potential clinical strategy for the targeted therapy and radiosensitivity in NPC. This evidence concerns the gene TP53 and nasopharyngeal carcinoma.