We applied WGS to analyze the clinical V. parahaemolyticus O4:K8 in southern China. WGS-SNPs phylogenetic analysis revealed the O4:K8 strains formed a distinct genetic lineage. Comparative genome analysis revealed the O4:K8 carried T3SS-1 and T3SS-2 elements. The WGS-bases analysis improves understanding epidemiology of this bacterium in food-borne disease surveillance.