Abstract: The TGF-β signaling pathway is a large family composed of numerous cytokines, which regulate many cellular functions, including cell growth, epithelial-mesenchymal transition, migration, differentiation and apoptosis, and plays a key role in the normal growth of tissues and organs, embryonic development and carcinogenesis.Once abnormal TGF-β signal transmission process occurs, a series of developmental defects and diseases are produced, such as occurrence of tumor, fibrosis of tissues and organs, connective tissue and bone diseases. By studying the role of TGF-β signaling pathway in the occurrence of different diseases, many therapeutic strategies targeting this pathway have been developed, such as monoclonal antibodies, receptor kinase inhibitors and antisense oligonucleotides. This review summarized the role of TGF-β signaling pathway in the occurrence of different diseases, and discussed the latest therapeutic strategies targeting this signaling pathway.