The results of this study demonstrate that upregulation of IRF1 after irradiation is required for radiation-increased PD-L1 expression and that KPNB1 mediates radiation-increased, cell-surface PD-L1 expression through both upregulation and nuclear import of IRF1 in HNSCC and LUAD cells. Here, IRF1 is linked to head and neck squamous cell carcinoma.