The H1N1 influenza A 2009 pandemic caused a global concern as it has killed more than 18,000 people worldwide so far. Studies that have found cross-neutralizing antibodies between the 1918 and 2009 pandemic flu elicit a basis of pre-existing immunity against the 2009 H1N1 virus in old population. The cross-reactivity occurs due to conserved antigenic epitopes shared between the two pandemic viruses. However, evolutionary mutation can enable the virus to elude human immunity system, making these antibodies probably no longer effective. In our study, we found that a possible mutation in B-cell epitope (the sequence PNHDSNKG) could be the chance for the virus to escape the 1918 antibody recognition. Hence, this finding can be helpful for further vaccine designs against the H1N1 2009 influenza A virus.