The findings of this study are as follows: [1] IR increased the activity of CBR1; [2] CBR1 inhibition increased the radiation sensitivity measured by clonogenic assay in vitro; [3] overexpression of CBR1 protected the HNSCC cells against IR; [4] CBR1 inhibition resulted in accumulated intracellular ROS levels leading to an increase in mitotic catastrophe and mitotic arrest; and [5] of the patients treated with radiation, patients with low CBR1 expression showed better prognosis. This evidence concerns the gene CBR1 and head and neck squamous cell carcinoma.