Although previous studies have identified DMRs in ESCC, tumor‐specific hyper‐DMRs were not found to be enriched in cancer‐related pathways.[22] Furthermore, a previous study primarily focused on the inverse relationship between DNA methylation and gene expression in ESCC.[23] Our study is the first to identify a positive correlation between the hypermethylation of UMRs and potentially oncogenic homeobox genes, thus highlighting the importance of DNA hypermethylation in regulating oncogenic genes in ESCC. The gene discussed is LBX1; the disease is esophageal squamous cell carcinoma.