Abstract: Objective To examine evolutionary characteristics of genome of novel avian influenza A H10N8 virus and to analyze the variation of the key amino acid sites of hemagglutinin (HA) and neuraminidase (NA). Methods First human infection case of novel avian influenza AH10N8 virus was diagnosed in Jiangxi province, China in December 2013.The variations in gene nucleotide and amino acid sequence of the novel avian influenza AH10N8 virus strain isolated were analyzed. Results The HA and NA gene sequence of the novel avian influenza A H10N8 virus strain (A/Jiangxi-Donghu/346/2013H10N8, shortly named JX346) showed high identity with A/duck/Hunan/S11205/2012 (H10N3)(97.0%) and A/mallard/Korea/1041/2010 (H10N8)(98.8%), respectively, and the six internal genes showed a more than 99.0% homology with avian influenza A H9N2 virus strain isolated from Jiangxi province.The amino acid sequence of HA at the hemagglutinin cleavage site of the JX346 was PELIQGR↓G and the HA with five glycosylation sites had substitutions (S199A, A331S, K431N)in the 130 loop.Meanwhile, there were seven glycosylation sites in the NA and three substitutions (S199A, A331S, K431N) in its antigenic epitopes.Selection pressure analysis indicated that 3 positively selected sites in major surface protein of the JX346 strain. Conclusion The novel avian influenza A H10N8 virus strain may be the reassortants of avian influenza A H10N3, H10N8 and H9N2N virus.The substitutions in the key sites of novel avian influenza A H10N8 virus may result in human infection.