Objective To establish adapted strain of seasonal H1N1 influenza virus in mice and infection model. Methods The mice model was induced by nose dropping method with influenza virus, by continuous passage in the lung tissue of BALB/c, to get the adapted strain of seasonal H1N1 in mice and seasonal influenza virus infection model, and the lung index and death rate was observed. Results After 8 times consecutive passages in the lung tissue of BALB/c, virulence of wild type seasonal H1N1 virus was increased to a high level. Genome sequencing and alignment indicated that the HA gene was mutated. Conclusion The virulent mouse-adapted variant A/Brisbane/59/2007-MA can be acquired from the avirulent A/Brisbane/59/2007 strain by continuous passage in the lung tissues of mice. Mutation of Thr to Ile at residue 89 of HA protein is the key virulence determinant.