Abstract: Influenza virus hemagglutinin (HA) is a key factor in the virus's invasion of host cells, involving the binding of the virus to target cells and the fusion of membranes. The proteolytic cleavage and activation of HA by host proteases are prerequisites for the virus to recognize host cells and initiate membrane fusion, and are also essential for viral infection of the host. This article summarizes the proteolytic activation of different subtypes of influenza virus HA by type Ⅱ transmembrane serine proteases, human tissue kallikreins, and other host proteases, and discusses their potential as targets for antiviral therapy.