Objective To investigate the drug resistance， molecular characteristics and prevalence of Vibrio parahaemolyticus O10：K4 in Guangdong Province from 2020 to 2022， and to provide evidence for the prevention and control of Vibrio parahaemolyticus infection.Methods Serological identification， drug susceptibility test， MLST typing and whole genome sequencing were performed for Vibrio parahemolyticus strains isolated from clinical samples of infected patients in Guangdong Province from 2020 to 2022. At the same time， the microbial gene annotation system was used to annotate the drug resistance genes and virulence factors.Results The 290 strains of Vibrio parahaemolyticus could be divided into 24 serotypes， of which O10：K4 accounted for 31.38% （91/290）. Drug susceptibility test of 91 strains of Vibrio parahaemolyticus O10：K4 showed that all strains were resistant to ampicillin and sensitive to other drugs. A total of 75 of 290 strains of Vibrio parahaemolyticus were selected for whole genome sequencing. The MLST typing and phylogenetic evolutionary relationship analysis showed that ST3 was the main sequence type of Vibrio parahaemolyticus O10：K4 （97.92%， 47/48） and was the closest genetic evolution to O3：K6. In addition， four novel Vibrio parahemolyticus sequence types were also identified in this study： ST3485， ST3486， ST3488 and ST3494. Vibrio parahaemolyticus O10：K4 has unique genetic markers of pandemic strains （toxRS/new+， orf8+， tdh+， and trh-） and carries multiple virulence genes， and the distribution of virulence genes is similar to that of serotypes O4：KUT and O3：K6.Conclusion The dominant serotype of Vibrio parahaemolyticus in Guangdong Province from 2020 to 2022 is O10：K4， which has similar molecular characteristics to O3：K6 and is sensitive to multiple antibiotics. Vibrio parahemolyticus sequences showed high diversity and clear phylogenetic clades， with ST3 as the local dominant clonal group.