In this study, the expression level of HMGB1 in the plasma exosomes of ESCC patients was higher than that of healthy individuals, and the radioresistance of ESCC patients with high HMGB1 expression (n = 11) was significantly higher than that of ESCC patients with low HMGB1 expression (n = 10). This evidence concerns the gene HMGB1 and esophageal squamous cell carcinoma.