Cats are susceptible to influenza A viruses and therefore may act as transmission vectors within households, posing a potential public health concern. Two novel reassortant H5N6 influenza viruses were isolated from cats in Zhejiang Province, Eastern China, in 2016. Both viruses were characterized by whole-genome sequencing with subsequent phylogenetic analysis and genetic comparison. Phylogenetic analysis showed that these viruses received their genes from H5N6, H9N2, and H7N9 influenza viruses isolated from China. These H5N6 viruses were able to replicate in mice without prior adaptation. Our results show that continued circulation of these viruses could endanger humans.