During December 2003 and March 2004, large scale epidemics of low-pathogenic avian influenza (LPAI) H5N2 occurred in poultry farms in central and southern Taiwan. Based on genomic analysis, these H5N2 viruses contain HA and NA genes of American-lineage H5N2 viruses and six internal genes from avian influenza A/H6N1 viruses endemic in poultry in Taiwan. After disappearing for several years, these novel influenza H5N2 viruses caused outbreaks in poultry farms again in 2008, 2010 and 2012, and have evolved into high pathogenic AI (HPAI) since 2010. Moreover, asymptomatic infections of influenza H5N2 were detected serologically in poultry workers in 2012. Therefore, we evaluated antigenicity and pathogenicity of the novel H5N2 viruses in ferrets. We found that no significant antigenic difference was detected among the novel H5N2 viruses isolated from 2003 to 2014 and the novel H5N2 viruses could cause mild infections in ferrets. Monitoring zoonotic transmission of the novel H5N2 viruses is necessary.