This study explored the epigenetic mechanism of FOXK1 in the development of estrogen receptor-positive breast cancer. Various molecular biology techniques were used, including immunoprecipitation, Western blotting, RNA interference, and quantitative PCR. The results demonstrated a clear relationship between FOXK1 and the REST/CoREST complex at the protein level and showed that decreasing FOXK1 expression also reduced the coREST complex. The study provides insight into a potential therapeutic approach for ER+ breast cancer by targeting this interaction.