Abstract: Spleen tyrosine kinase (Syk) is a cytoplasmic non-receptor protein tyrosine kinase that is mainly expressed in hematopoietic cells. It not only plays a vital role in immune receptor signaling, but also regulates other different biological functions, including cell adhesion, proliferation, osteoclast maturation, and platelet activation. In recent years, Syk has become an attractive drug target in hematological malignancies, autoimmune, inflammation and other diseases. This article introduces the structure and activation mechanism of Syk as well as the relationship between its signaling pathways and diseases, and reviews the clinical research progress of oral small molecule Syk inhibitors, aiming to provide reference for further research and application.