Since the strain A/goose/Guangdong/1/1996(H5N1) emerged in China in 1996, H5 viruses have spread to Eurasia, Africa and North American and outbreaks have occurred frequently. After 2010, new H5 reassorted with different NA subtypes (H5Nx lineages, i.e., H5N2, H5N6, and H5N8) emerged through multiple genetic reassortments of different subtype viruses within wild birds and domestic populations ( 1 ). In recent years, H5Nx lineages of the avian influenza virus (AIV) with genomic reassortments have proved the capacity for zoonotic spread and posed a continuous threat to poultry and human beings. Among these AIVs, the reassortant H5N6 virus that was first reported in 2013 and the first reported H5N6 case of human infection was dated in 2014. Until January 21, 2022, a total of 67 laboratory-confirmed cases of human infection with H5N6 virus were confirmed. Specially, there were 39 human cases have been occurred in China since 2021.