To our knowledge, our study for the first time systematically elucidates the impact of hypoxia on ligand-independent EGFR phosphorylation and the endocytosis, intracellular fate, and downstream signaling of EGFR in human cancer cells harboring wt EGFR, thus revealing a functional link between these two characteristic events in tumor progression. The gene discussed is EGFR; the disease is neoplasm.