In this study, we investigated a poor‐prognostic epithelia‐immune dual expression program in ESCC tumor cells characterized by overexpression of immune cells signaling mediators (MHC class II surface receptor CD74, HLA‐DR, and TYROBP), epithelial‐mesenchymal transition related genes (Glucose metabolism regulator HK3, Iron metabolism regulator FTL), and cell adhesion and migration related gene (C1Q, ADGRE3, CTSZ, and PSAP). Here, HK3 is linked to neoplasm.