We found that: 1) knockdown of MED1 sensitizes otherwise resistant BT474, ZR75-1 and MCF-7F cells to fulvestrant treatment; 2) MED1 knockdown works cooperatively with fulvestrant to inhibit the expression of endogenous ERα target genes and cell cycle progression; 3) knockdown of MED1 affects the recruitment of RNA polymerase II and transcriptional corepressor HDAC1 on the endogenous ER target gene promoter in the presence of fulvestrant; 4) down-regulation of MED1 in combination with fulvestrant dramatically inhibits the growth of orthotopic tumor xenografts in vivo. The gene discussed is MED1; the disease is neoplasm.