Abstract: In May 2013, the first case of human infection with avian influenza A (H6N1) virus was reported in Taiwan, and it was the first direct evidence of human infection with H6N1 virus in the world. The virus might be derived from different H6N1 lineages virus circulating in Taiwan. Furthermore, some important amino acid substitutions were found in the receptor-binding loci of HA protein of the new virus, which is considered to be associated with the higher affinity to the human-like receptor. Substitutions which may enhance the pathogenicity to mammals were also observed in the virus. This paper summarizes the pathogenicity, epidemiology and the receptor-binding specificity of H6N1 viruses, which would be helpful to the development of strategies for the future disease control and pandemic preparedness.