In this study, by using a combination of bioinformatics tools, de novo and acquired tam-resistant breast cancer cell lines, and human breast cancer patient datasets, we have identified miRNA-205 as a key regulator of MED1 expression and activation in mediating the endocrine resistance of human breast cancer, and further determined its roles and underlying molecular mechanisms in both in vitro and in vivo orthotopic xenograft mouse models. Here, MED1 is linked to breast carcinoma.