In order to reveal variation and revolution of NP genes of human avian H_5N_1 influenza virus strains,the NP gene of a human avian H_5N_1 influenza virus strain in Guangdong was sequenced and the global NP genes of strains were retrieved.The sequences were analyzed by DNAStar 5.0,and the evolu- tionary speed was studied with reference to the epidemiological data.It was found that NP genes of 45 strains during 1997-2006 were homologically classified into three groups:strains in 1997-1998,strains in 2004-2005 and strains from 2003 to 2006.There were 35 substitutions in NPs in all strains accounting for a ratio of 7.03%(35/498).An additional glycoprotein domain(NGT_(430-432))was found in NP genes in the strains of 2003-2006,the mutation of N_(370)S in GD-01-06 resulted in occurrence of one more glyco- protein domain(NES_(368-370)).In the synonymous variation,K_s values in NP were 2.03×10~(-5)-2.55×10~(-5) Nt/d and K_a values in NP were 1.58×10(-6)-3.10×10~(-6) Nt/d.There didn′t exist obviously selective pres- sure.An additional glycoprotein domain in every strain of 2003-2006 and one more in strain GD-01-06 might change the antigenicity of human avian H_6N_1 influenza virus.The variation on human avian H_5N_1 influenza strains occurred frequently in the natural world,which would result in high probability of hu- man-human transmission along with the natural evolution of the virus. In order to reveal variation and revolution of NP genes of human avian H_5N_1 influenza virus strain, the NP gene of a human avian H_5N_1 influenza virus strain in Guangdong was sequenced and the global NP genes were recorded. The sequences were analyzed by DNAStar 5.0 , and the evolu- tionary speed was studied with reference to the epidemiological data. It was found that NP genes of 45 were homologically classified into three groups during 1997-2006: Excerpts from 1997-1998, in 2004-2005 and from 2003 to 2006. There were 35 substitutions in NPs in all accounting for a ratio of 7.03% (35/498). An additional glycoprotein domain (NGT_ (430-432)) was found in NP genes in the strain of 2003-2006 , the mutation of N_ (370) S in GD-01-06 resulted in one more glyco-protein domain (NES_ (368-370)). In the synonymous variation, K_s values ​​in NP were 2.03 × 10 ~ 5) -2.55 × 10 ~ (-5) Nt / d and K_a values ​​in NP were 1.58 × 10 (-6) -3.10 × 10 ~ (-6) Nt / d.There did not exis t obviously selective pres- sure. An additional glycoprotein domain in every strain of 2003-2006 and one more in strain GD-01-06 might change the antigenicity of human avian H_6N_1 influenza virus. The variation on human avian H_5N_1 influenza mutation occurred frequently in the natural world, which would result in high probability of hu- man-human transmission along with the natural evolution of the virus.