Current data suggest that NRF2 hyperactivation (NRF2high) may promote lymphatic metastasis of ESCC by affecting the extracellular matrix (ECM), epithelial–mesenchymal transition (EMT), lymphangiogenesis, immune evasion, metabolic programming, and Hippo signaling. This evidence concerns the gene NFE2L2 and esophageal squamous cell carcinoma.