CRNN (Cornulin) gene has a strong tumor suppressive ability in which its arrest cell cycle at G1/S checkpoint in Esophagus squamous cell carcinoma (ESCC) but it has been studied that it is down regulated in tumor tissues without specific pathogenic mutation, but it is appeared that it interact with tobacco smoking that contribute to the risk of developing HSCC [44]. Here, CRNN is linked to esophageal squamous cell carcinoma.