Li et al. found that androgen/ androgen receptor (AR) signaling mediated promotion, as well as estrogen/ estrogen receptor (ER) signaling mediated protection, of HCC, are driven by the Foxa1/Foxa2-dependent recruitment of ER-α and AR to target genes in a chemical-induced hepatocarcinogenesis mouse model. Here, ESR1 is linked to hepatocellular carcinoma.