Our current study shows that NRF2-silencing suppresses hypoxia-inducible HIF-1α accumulation in breast cancer cells, and thereby inhibits the HIF-1α-mediated metabolic adaptation, including glycolysis activation, PPP facilitation, and autophagy stimulation, which eventually impairs the viability of NRF2-silenced cancer cells in hypoxic environment. The gene discussed is HIF1A; the disease is breast cancer.