Transforming growth factor beta (TGF-β) promotes cancer growth in late stage cancers. To inhibit the TGF-β pathway， we investigated a tumor-targeting TGF-β receptor blocker， TTB， and its role in tumor progress. The targeted TTB comprised of the extracellular domain of the TGF-β receptor II， the endoglin domain of TGF-β receptor III， and the human immuno-globin IgG1 constant fragment (Fc). To enhance tumor microenvironment targeting， a RGD peptide was fused at the N-terminal of TTB. The targeted TTB exhibited potent TGF-β neutralization activities， and inhibited cancer cell migration and invasion as well as colony formation. In xenograft models， the TTB had potent tumor inhibition activities. The TTB also attenuated the TGF-β1-induced Smad2 phosphorylation and epithelial to mesenchymal transformation (EMT)， and suppressed breast cancer metastasis. Thus， the TTB is an effective TGF-β blocker with a potential for blocking excessive TGF-β induced pathogenesis .