Collectively, our study verified the NRAGE, with anti-oncogene and oncogene contradictory roles, was regarded as an oncogene due to the functions that accelerated proliferation, anti-apoptosis effect, more malignant migration and invasion, and accumulation of IR resistance by triggering Wnt/β-catenin signaling pathway in ESCC cells in 2D and 3D levels. Here, MAGED1 is linked to esophageal squamous cell carcinoma.