Human infection with highly pathogenic avian influenza (HPAI) caused by certain strains of avian influenza A viruses, such as H5N1 and H7N9, results in severe acute respiratory disease with a high mortality rate, among which the former is pathogenic to birds.[1] In recent years, HPAI H5 has spread globally, causing human infections. The first reported case of bovine H5N1 infection, which was subsequently transmitted to humans, garnered significant international attention. Drawing on the historical influenza pandemic experience and biological characteristics of the virus, under specific conditions, such as reassortment with human and swine influenza viruses, avian influenza viruses (AIV) may achieve efficient human-to-human transmission, potentially leading to a global pandemic. Here, we aimed to review the historical trends of H5N1 avian influenza infections in humans and the recent developments in epidemiological situations, evaluate the transmission risk of H5N1 avian influenza, and propose avian influenza control recommendations for public health decision-making.