The aims of this study were to give a comprehensive virological and epidemiological overview of the past four influenza seasons (2016–2020), to assess the frequency and distribution of the influenza virus types and subtypes circulating in North Macedonia as well as to carry out molecular and phylogenetic analyses of the HA and NA gene sequences of influenza A(H1N1)pdm09, A(H3N2), B/Victoria and B/Yamagata from patients from the sentinel surveillance. This evidence concerns the gene XK and influenza.