Exposure of tumor cells to Transforming Growth Factor β (TGF-β) induces epithelial-mesenchymal transition (EMT) and generates cells with a stable cancer stem cell (CSC) phenotype, which promotes metastasis in advanced malignancy. TGF-β promotes EMT by a combination of Smad-dependent transcriptional events and Smad-independent effects. A role for the microRNA (miRNA) in TGF-β/Smad signaling has recently been appreciated. However, the role of microRNAs in the noncanonical TGF-βsignalings remains illusive. Our previous study found that breast CSCs had elevated miR-106b, a member of miR-106b family,thus, the role of miR-106b in TGF-βinduced EMT was further investigated. Here, we profiled that miRNA signature of EMT induced by TGF-βin normal human mammary gland epitherial cells. We further demonstrated that TGF-β1 transcriptionally upregulates miR-106b via c-jun. miR-106b mediates TGF-β-induced proliferation, EMT, migration and invasion as well as self-renew. Morever, breast cancer metastasis-suppressor 1-like (BRMS1L) and Retinoblastoma1(RB1) are negatively regulated by miR-106b and contribute to TGF-β-induced phenotypes. In addition, oncogeneic function of miR-106b was also validated in mouse models and clinical correlation studies.