Estrogen receptor alpha (ER alpha) expression is a risk factor for breast cancer. HDAC inhibitors have been demonstrated to down-regulate ER alpha expression in ER alpha-positive breast cancer cell lines, but the molecular mechanisms are poorly understood. Here, we showed that HDAC inhibitors decrease the stability of ER alpha mRNA, and that knockdown of HDAC3 decreases the stability of ER alpha mRNA and suppresses estrogen-dependent proliferation of ER alpha-positive MCF-7 breast cancer cells. In the Oncomine database, expression levels of HDAC3 in ER alpha-positive tumors are higher than those in ER alpha-negative tumors, thus suggesting that HDAC3 is necessary for ER alpha mRNA stability, and is involved in the estrogen-dependent proliferation of ER alpha-positive tumors. Crown Copyright (C) 2013 Published by Elsevier Inc. All rights reserved.