p53 gain-of-function (GOF) mutations can lead to new tumor-driver activities, however it remains unknown whether different mutants act through similar mechanisms in vivo. In a proteomic screen, we identified BACH1 as a cellular factor that recognizes the p53 DNA binding domain depending on its mutation status. BACH1 specifically interacts with p53R175H but fails to bind wild type p53 or other hot-spot mutants. Interestingly, p53R175H acts as a repressor for BACH1-dependent ferroptosis by abrogating BACH1-mediated downregulation of SLC7A11 to promote tumor growth; conversely, p53R175H coactivates BACH1-dependent tumor metastasis by upregulating pro-metastatic gene expression. Mechanistically, p53R175H-mediated bidirectional regulation of BACH1 function is dependent on its ability to recruit the histone demethylase LSD2 to target promoters and differentially modulating transcription. Our study also provides evidence that each p53 mutant may act through a distinct GOF mechanism thus, have significant implications regarding how to eliminate the GOFs of specific p53 mutant for cancer therapy.