Gastroesophageal reflux disease ( GERD) is a common disease in gastroenterology, and clinical manifestations are prone to recurrent attacks. It is considered a risk factor for the development of esophageal adenocarcinoma( EAC). Family studies have shown that GERD heritability is approximately 30%, COL3A1 and ABAT genes are significantly associated with genetic risk. Several genes, such as the IL-1 gene cluster, GNB3 and GSTP1, are strongly associated with the risk of GERD. Mutations in TP53 and single nucleotide polymorphisms of EGF, MMP, CCND1, CDX2 and COX-2 cause genomic instability and promote the development of Barrett’s esophagus and EAC in some individuals. This article reviews the role of molecular biology in the occurrence and development of GERD into EAC.