Objective To conduct genetic variation monitoring of influenza A(H1N1)virus in Futian dis-trict of Shenzhen city through evolutionary analysis,so as to provide a theoretical basis for the scientific pre-vention and control of H1N1.Methods Throat swab specimens from influenza surveillance sentinel hos-pitals and outbreaks of influenza cases were collected and isolated in the Futian district of Shenzhen for nucleic acid detection in the first quarter of 2023.The H1N1 whole gene sequences of 41 isolated H1N1 strains were determined by high-throughput sequencing,and the whole genome single nucleotide polymor-phisms(SNPs)were extracted using Snippy software.Multiple sequence alignment was performed using Muscle software,and hemagglutinin(HA)and neuraminidase(NA)evolution trees were constructed using Iqtree software.The molecular epidemiological characteristics of the viruses were analyzed by comparing them with sequences from all over the world and the vaccine strains recommended by WHO.Results The sequencing achieved an average genome coverage of 98.06%for the 41 H1N1 strains,confirming data reliability.A comparison with strains from around the world showed that the local strains had a high degree of homology with those from Southeast Asia.Using vaccine strain A/Wisconsin/67/2022 as a reference,local strains mutated at HA antigenic variation sites S154P,R159K,E277D,A294T,D373E,and H468N,while NA antigens mainly mutated at V13I,S200N,L339S,and N469X.The mutations S154P and R159K were located in the Sa region,and these variations might be associated with antigenic drift or immune escape.Conclusions The genetic diversity and antigenic variations of the 2023 H1N1 influenza virus in Shenzhen's Futian district may influence vaccine effectiveness.Continuous monitoring is crucial for guiding public health interventions and vaccine strain selection.