Our study revealed that HS-173 could efficiently suppress TGF-β-induced migration, invasion, and metastasis by inhibiting EMT process through the regulation of PI3K/AKT/mTOR and Smad2/3 signaling pathways, suggesting that HS-173 is a potential candidate for advanced stage treatment of pancreatic cancer with metastasis. This evidence concerns the gene SMAD2 and pancreatic neoplasm.