H10 subtype avian influenza viruses were endemic in wild and domestic avian species worldwide. Strikingly, it frequently crossed the species barrier to infect mammalian hosts. Human infection with H10N3 and H10N8 were reported previously. Recently, a 63-year-old woman from Anhui province of China who died from a mixed infection of H3N2 and H10N5 influenza viruses, which have drawn widespread public health attention. Here, we perform the evolutionary dynamics of H10N5 influenza viruses of bird- and human-origin worldwide, and found that wild bird-origin H10N5 influenza viruses from China did not cluster together with human-origin H10N5 influenza viruses, while grouped together with LPAIV gene pools circulating in wild birds that derived from other Eurasian countries. Human-derived H10N5 virus is a novel reassortant, which frequently reassorted with wild bird-derived influenza viruses, and in turn, spillover into humans. Collectively, our results suggested that H10 subtype influenza viruses continuously pose threat to public health.