Abstract: ObjectiveTo reveal characteristic and evolution on HA geoe of human H₅N₁ avian influenza by analyzing variation of the nucleotide sequence of HA gene of human H5Nl avian influenza.MethodsHA gene of Guangdong strain was sequenced and others global HA nucleotide sequences of human H5Nl avian influenza from Internet and their variation were clustered and compared and analyzed with SPSS 11.0 and DNA Star 5.0.ResultsForty-two HA genes of human H₅N₁ avian influenza in 1997～2006 were clustered into three groups.Eighty～nine amino acids of HA gene were substituted and ac2 counted for 15.7% (89/568).HA gene increased one glycoprotein domain in 170～172 sites(NST/S)in 2003～2006.In the synonymous varimion,Ks in HA gene was between 1.99×10^-5～2.58×10^-5 and the evolutionary linear regression equation was Y=4.84×10^-9 X+1.048×10^-5.Meantime,Ks was more than Ka in same strain and Ks/Ka value showed that there was not selective pressure in HA gene evolution.H₅N₁ strain evolution was divided into three clusters,one for strains in 1997～1998,another for strains in 2003～2005 except for strains from China,third for strain from China in 2005～2006.The variation of strain HK-213-03 showed their transitions between 1997 and 2004,and the variations of the amino acids on HA in TL-L2004-04 was remarkable.ConclusionThere was the differences between HA of strains in 2003～2006 and strains in 1997 and one more glycoprofein domain might increase the viral pathogenicity;it was worth noticing variations of the amino acids on HA in TL-L2004-04.Human H₅N₁ strains evolve frequently in the natural environment,but were not subject to avian or human immunological pressure.However,the probabilities were great that H₅N₁ strains possess of humanto human transmittion as the natural evolution.The antigenicity of HA gene was needed to consider in vaccine of different human H₅N₁ strains.