Based on bulk RNA-seq data and scRNA-seq data analyses, 18 DE-TrpGs (ALDH9A1, ALDH3A2, ADH1B, AOX1, MAOA, ECHS1, ALDH2, ACAT1, HAAO, ALDH7A1, HADHA, AKR1A1, CYP4X1, INMT, CYP2U1, CAT, HADH, and NMNAT1) were screened in ESCC, then incorporated into a LASSO regression model to select the diagnostic TrpGs in ESCC. This evidence concerns the gene CYP2U1 and esophageal squamous cell carcinoma.