Abstract: OBJECTIVE To explore the virulence, drug resistance mechanisms and molecular epidemiological characteristics of the clinical isolates of Klebsiella pneumoniae in Foshan and Qingyuan. METHODS The clinical isolates of non-repetitive K. pneumoniae were collected from The First People's Hospital of Foshan and Qingyuan People's Hospital from 2023 to 2025 and were retrospectively analyzed. The bacterial isolates were identified by Vitek 2 compact automatic microorganism analysis system, and the in vitro antimicrobial susceptibility testing was performed. The drug resistance phenotypes were determined by modified carbapenem inactivation method (mCIM) combined with ethylene diamine tetraacetic acid (EDTA)-enhancing carbapenem inactivation method (eCIM) and disk potentiation test. The carbapenems resistance genes and virulence genes were detected by means of polymerase chain reaction (PCR) amplification and whole genome sequencing (WGS). The high-viscosity phenotypes of strains were screened out by string test. The strains were further validated through seroresistance assay, and the virulence characteristics of the strains were analyzed by Galleria mellonella infection model. RESULTS Among the 60 strains of K. pneumoniae, 14 were positive for the string test. The antimicrobial susceptibility phenotype test showed that there were 28 strains positive for serine hydrolase and 2 strains positive for metallo-β-lactamase. There were 55 strains carrying mucin phenotype regulatory gene A2(rmpA2), 58 strains carrying ironophore receptor protein A gene(iutA), 58 strains carrying with iron uptake chelation system protein A (iucA), and 54 strains carrying iron-regulated outer membrane receptor protein N(iroN). A total of 14 types of plasmid replicons were detected by whole genome sequencing, IncFII(pHN7A8), repB and IncR were the predominant types of plasmids. Among the 5 strains of hypervirulent Klebsiella pneumoniae (hvKP), there was 1 strain with significant seroresistance and 4 strains with medium serum sensitivity. G. mellonella infection assay showed that the median lethal dose values ranked in the following order:carbapenem-resistant Klebsiella pneumoniae (CRKP) > carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) > hvKP. CONCLUSIONS The KPC carbapenemase-producing CRKP strains are prevalent in Foshan and Qingyuan. High detection rates of drug resistance genes, virulence genes and plasmid replicons in the K. pneumoniae strains indicate that it should maintain vigilant to the risk of co-transmission of high drug resistance and virulence among the K. pneumoniae strains in the area.