When introduced into MDA-MB-231 cells, ESR1 counteracts the tumor suppressor roles of FOXA1 by altering the FOXA1-regulated gene transcription and the two proteins together maintain the tumor progression in vivo. Our cumulative results suggest that FOXA1 suppresses the basal breast cancer cells with FOXA1-low expressing status independent of ESR1 by inducing apoptosis and inhibiting cell proliferation, thereby implicating its potential therapeutic role in this group of breast cancer.