Objective To compare the clinical and molecular epidemiological characteristics between NDM-1-procucing and KPC-2-procucing carbapenem-resistant Klebsiella pneumoniae (CRKP). Methods Clinically isolated non-repetitive CRKP strains from children in a children's hospital from 2017 to 2020 were retrospectively analyzed. Basic clinical characteristics of the patients from whom strains were detected were obtained by referring to their medical records. Antimicrobial susceptibility testing and multilocus sequence typing (MLST) analysis on CRKP were performed. Clinical and molecular epidemiological characteristics of NDM-1-procucing and KPC-2-producing CRKP were compared. Results A total of 164 CRKP strains were collected from 2017 to 2020, among which 96 strains carried bla_NDM-1 and 68 strains carried bla_KPC-2. NDM-1-producing CRKP were mainly from neonatal department, while KPC-2-producing CRKP were mostly from non-neonatal departments. There were statistically significant differences in specimen sources, patient's age, department distribution, and prognosis between the two groups (all P < 0.05). NDM-1-producing CRKP strains were mainly ST 17 and ST 278, accounting for 40.63% and 18.75% respectively, while KPC-2-producing CRKP strains were mainly ST 11 (73.53%). Resistance rates of KPC-2-producing CRKP to cefepime, aztreonam, imipenem, amikacin, gentamicin, furanotoin and fosfomycin were higher than those of NDM-1-producing CRKP, all with statistical significance (all P < 0.05). Conclusion Clinical and molecular epidemiological characteristics of NDM-1-procucing and KPC-2-producing CRKP strains are different. KPC-2-producing CRKP strains show more serious antimicrobial resistance and poor prognosis in patients, thus should be paid more attention in clinic and infection control.