Objective To analyze the molecular epidemiological characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP) in a hospital in Hainan Province, explore the differences in the distribution of resistance genes and virulence factors between hypervirulent CRKP (hv-CRKP) and non-hv-CRKP, analyze the clinical significance, and provide basis for optimizing treatment and prevention strategies. Methods CRKP strains isolated from a hospital in Hainan Province from July 2023 to June 2024 were collected retrospectively. Their resistance phenotypes were detected by antimicrobial susceptibility testing. Carbapenemase genes (KPC-2, NDM-1, IPM) and virulence factors (rmpA/rmpA2, iucA, iroB, etc.) were detected by polymerase chain reaction (PCR). Department source, specimen distribution, and resistance-virulence characteristics were analyzed. Results A total of 76 strains of CRKP were isolated, with an overall isolation rate of 7.7% (76/985). The strains were mainly distributed in the intensive care unit (ICU) (28.9%) and neurosurgery ICU (23.6%), with the highest proportion of strains isolated from respiratory tract specimens (60.5%). The resistance genes were mainly KPC-2 (72.4%) and NDM-1 (21.1%), and the virulence factors mrkD (type Ⅲ pili, 85.5%) and fimH (type Ⅰ pili, 84.2%) were commonly presented. Among 76 strains of CRKP, 39 strains (51.3%) met the criteria for hv-CRKP and all carried KPC-2 gene (100%). The detection rates of resistance genes and virulence factors rmpA2 (97.4%), iucA (100%), and iroB (89.7%) were all higher than those of non-hv-CRKP strains (KPC-2, 43.2%; rmpA2, 0; iucA, 8.1%; iroB, 13.5%). The main characteristics of hv-CRKP was the combination of KPC-2 resistance gene and rmpA2+iucA+iutA+iroB virulence factors (64.1%). Antimicrobial resistance phenotype of hv-CRKP was different from non-hv-CRKP. hv-CRKP presented higher susceptibility rates to aminoglycosides and compound sulfamethoxazole than non-hv-CRKP. Conclusion The proportion of hv-CRKP and non-hv-CRKP strains in this hospital is comparable. hv-CRKP is characterized by carrying the KPC-2 resistance gene in combination with rmpA2+iucA+iutA+iroB virulence factors, and the proportion of strains carrying multiple virulence factors is higher than that of non-hv-CRKP. Both are generally resistant to β-lactams and quinolones. hv-CRKP has lower resistance rates to aminoglycosides and compound sulfamethoxazole than non-hv-CRKP. Its advantage of aminoglycoside susceptibility provides a new treatment option. It is recommended to guide differential medication through molecular typing and strengthen infection control measures in ICU to curb the spread of antimicrobial-resistant bacteria.