In esophageal squamous cell carcinoma, the cancer-associated fibroblasts (CAFs) were found to produce high expression of chemokine CXCL1, which promotes radiotherapy resistance in vitro and in vivo in ESCC through an overregulated expression of DNA damage repair proteins (e.g., p-ATM, Rad50, p-Chk2, Ku80, and DNA-PKcs) and the Mek/Erk signaling pathway activation, as well as an increase of γ-H2AX protein. This evidence concerns the gene H2AX and esophageal squamous cell carcinoma.