In order to verify the biological effects and mechanism of FOXK1 in ESCC, in the present study, we assessed the expression of FOXK1 in ESCC cell lines and tissues, examined its function in regulating oncogenesis and radiosensitivity in ESCC cells, and analyzed the target genes of FOXK1 and their roles in mediating ESCC progression and response to radiation. The gene discussed is FOXK1; the disease is esophageal squamous cell carcinoma.