In this study, we firstly identified HDAC3 phosphorylation at both Y328 and Y331 residues in response to EGF stimulation in an EGFR-dependent and c-Src-dependent manner, and found that the phosphorylation of HDAC3 significantly enhanced its deacetylase activity, accelerating the invasiveness of breast cancer cells. The gene discussed is HDAC3; the disease is breast cancer.