High expression of estrogen receptor α (ERα) is associated with a poor prognosis that correlates closely with cellular proliferation in breast cancer. However, the exact molecular mechanism by which ERα controls breast cancer cell proliferation is not clear. Here we report that ERα regulates the cell cycle by suppressing p53/p21 and up‐regulating proliferating cell nuclear antigen (PCNA) and proliferation‐related Ki–67 antigen (Ki–67) to promote proliferation of MCF–7 cells. In addition, 17–β–estradiol (E2) enhances ERα‐induced proliferation of MCF–7 cells by stimulating expression of PCNA and Ki–67. Knockdown of ERα significantly affects PCNA/Ki–67 and p53/p21 expression. Furthermore, ERα inhibits the transcriptional activity of p53/p21 in an estrogen response element‐dependent manner. More importantly, we provide new evidence that ERα mediates proliferation of MCF–7 cells by up‐regulating miR–17 to silence the expression of p21. Thus, these data provide new insights into the underlying effect of ERα on breast cancer proliferation. Model for how estrogen receptor α (ERα) regulates MCF‐7 cell proliferation by p53‐p21‐PCNA‐E2F1 pathway.