Background Notch signaling pathway, which is highly conservative, was considered to play an important role in the cell differentiation, cell proliferation and organ development. Additionally, Notch signaling pathway could respond to the emergency events in cells, and then participate in the mechanism of organ injury. Objective To review the recent research progression on the role of Notch signaling pathway in vital organ injury. Content This review introduces the components of the Notch signaling pathway and its role in injury of the vital organs, such as brain, heart, lung, liver, and kidney. Trend Notch signaling pathway may play different roles in each organ injury. The further advanced studies focused on Notch signaling pathway could provide new idea and methods for organ injury prevention and organ function protection.