These results indicated that IR-NC-Exos could reverse irradiation-induced degradation of Cyclin B1 and CDK1, help to eliminate G2/M arrest and promote cell cycle progression, while IR-shHMGB1-Exos could arrest ESCC cells in G2/M phase by reducing the expression of Cyclin B1 and CDK1, which reversed radioresistance. Here, CDK1 is linked to esophageal squamous cell carcinoma.