High-throughput screening identified febrifugine derivatives as NRF2 inhibitors. The febrifugine derivative halofuginone (HF) suppresses NRF2 protein accumulation. HF represses protein synthesis via an amino acid starvation response. HF enhances the sensitivity of NRF2-addicted cancer cells to anti-cancer drugs. HF serves as a chemo-sensitizer of NRF2-addicted cancer cells.