The 2017 Hong Kong influenza A(H3N2) summer season was unexpectedly severe. However, antigenic characterization of the 2017 circulating A(H3N2) viruses using ferret antisera did not show significant antigenic drift. We analyzed the hemagglutinin amino acid sequences of A(H3N2) virus circulating in Hong Kong in 2017, and found that viruses with hemagglutinin N121K substitution, which was rare before 2017, emerged rapidly and dominated in 2017 (52.4% of A[H3N2] virus in 2017 contains N121K substitution). Microneutralization assay using archived human sera collected from mid-2017 showed that the geometric mean microneutralization titer was 3.6-fold lower against a 2017 cell culture-grown circulating A(H3N2)-N121K virus (3391/2017 virus) than that against the cell culture-grown 2016-2017 A(H3N2) seasonal influenza vaccine-like vaccine virus (4801/2014 virus) (13.4 vs 41.8, P?