Recently, the first human case of acute respiratory distress syndrome caused by the H3N8 subtype avian influenza virus (AIV) (A/Henan/4-10CNIC/2022, Henan4-10) was documented in this journal. The H3N8 subtype AIV was isolated from 4-year-old children who had contact with chickens and crows in Henan, China. Meanwhile, this journal has previously documented that wild bird origin H3N8 AIV has the binding affinity to both a-2,3 and a-2,6 receptors. Their results suggested that H3N8 AIV can replicate well and exhibit pathogenicity in BALB/c mice without prior adaptation. Previous surveillance studies conducted in wild birds and live bird markets indicated that the H3N8 subtype is one of the most common subtypes in domestic ducks and has undergone extensive reassortment with other endemic subtypes in waterfowl. Moreover, the H3N8 virus is one of the best mammalian adapted AIVs and has been reported in various species, including dogs, horse, pig, harbor seal, grey seal, and donkeys. Those studies suggested that predominantly H3N8 AIVs are inclined to cross species barriers and pose a significant threat to human and animal health.