The results of the multifactorial Cox regression model showed that TNM stage (stage III-IV) (HR = 1.961, 95% CI: 1.125–2.768), tumor hypofractionation (HR = 1.453, 95% CI: 1.034–2.857), presence of lymph node metastasis (HR = 1.499, 95% CI: 1.025–2.851), and DACH1 methylation (HR = 1.718, 95% CI: 1.067–2.596) may increase the risk of insensitivity to radiotherapy in patients with esophageal cancer (P < 0.05). The gene discussed is DACH1; the disease is esophageal cancer.