In this study, we investigated the existence of hot spot mutations in exon 19 and 21 of EGFR in Chinese ESCC patients with another sensitive method based on denaturing high performance liquid chromatography (DHPLC) as well as direct sequencing, simultaneously, and screened the status of K-RAS gene (codon 12/13) mutation by direct sequencing as well. This evidence concerns the gene KRAS and esophageal squamous cell carcinoma.