Abstract:H5N8 subtype highly pathogenic avian influenza virus (HPAIV) has spread to Asia, Europe, Africa, the Americas, and other countries and regions with the migration of wild birds and commercial trade activities. H5N8 HPAIV caused two waves of pandemic in 2014-2015 and 2016-2019, and the third wave has broken out, leading to the death of a large number of poultry and wild birds and serious economic loss. Previous studies have shown that mutation can enhance the virulence of the virus to mammals such as canines, mice, and minks. The first human infection event was reported in February 2021, which is of important public health significance. This article reviewed the global epidemic situation of the H5N8 HPAIV in recent years, and discussed its origin and hazards. We suggest strengthening the active surveillance of AIV in wild birds, especially migratory birds, and performing early warning to reduce economic loss and threats to human health.