Dong et al. (2014) have demonstrated that the upregulated miR-21 reduced the PTEN expression in TNBC. In this study, using MDA-MB-231 and BT549 cells, we firstly demonstrated the expression of PTEN could be dose-dependently up-regulated by fisetin at mRNA and protein levels, along with the reduction of p-Akt and p-GSK-3β activation. And in vivo, with the breast cancer xenograft model bearing MDA-MB-231 cells, we further found that fisetin also apparently up-regulated the expression of PTEN and inhibited p-Akt in primary tumor tissues. This evidence concerns the gene AKT1 and neoplasm.