Objective To understand the drug resistance, virulence and epidemiological characteristics of clinically isolated carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP). Methods Clinically isolated carbapenem-resistant Klebsiella pneumoniae (CRKP) from a teaching hospital in Anhui Province from January 2018 to December 2020 were collected, their clinical characteristics were analyzed. Bacterial trains were identified by time-of-flight mass spectrometry, CR-hvKP was screened out by string test and virulence gene detection, carbapenem-resistant non-hypervirulent Klebsiella pneumoniae (CR-non-hvKP)isolated in the same ward or at a similar time with CR-hvKP was as control group according to 1:1 ratio. The whole genome sequencing was used to analyze the capsule serotype, drug resistance, virulence gene and ST typing of CR-hvKP and CR-non-hvKP in control group, difference between two groups of strains was compared. Results A total of 512 CRKP strains were isolated, including 30 CR-hvKP strains and 482 CR-non-hvKP strains. Most patients with CR-hvKP infection were the elderly (n=20, 66.67%), with respiratory diseases (n=29, 96.67%), digestive system diseases (n=12, 40.00%), septic shock (n=10, 33.33%), invasive treatment (n=23, 76.67%) and high mortality (n=20, 66.67%). Resistant rates of CR-hvKP to most commonly used antimicrobial agents were>90%, to tegacyclin was 3.33%, and all were sensitive to polymyxin B. There was no statistically significant difference in resistance between CR-hvKP and CR-non-hvKP (P>0.05). Sequencing results showed that the major carbapenem-resistance gene carried by CR-hvKP was bla_KPC-2 (n=28, 93.33%). Detection rate of resistant genes SHV-11, mph(A) and armA were lower than those of CR-non-hvKP strains. Detection rates of virulence genes iucA, iutA, fimF, fimH and mrkD carried by 30 CR-hvKP strains were all 100%, which was higher than those of CR-non-hvKP strains, with statistically significant difference (all P < 0.05). Detection rate of ST11-K64 in CR-hvKP strains was higher than that in CR-non-hvKP strains (76.67% vs 40.00%, P < 0.05). Conclusion KPC-2-producing ST11-K64 CR-hvKP is the main prevalent strain in the hospital, which carries more virulence and drug resistance genes and has a high mortality. The elderly and intensive care unit patients should be paid more attention in clinic.