Objective To investigate the trend and mechanism of drug resistance of carbapenem-resistant Klebsiella pneumoniae (CRKP) by the epidemiol. data. Methods The CRKP isolated from Shanxi Bethune Hospital from Jan. 2018 to Jan. 2019 were collected for identification, drug sensitivity test and phenotype screening. The major carbapenem-resistance genes [class A (KPC), class B (NDM, IMP, VIM), class D (OXA-48)] and outer membrane pore protein (OmpK 35, OmpK 36) were detected by PCR. The relative quant. anal. of gene expression was performed by real-time quant. PCR. Results The separation rate of CRKP was 4.91% . The highest separation rate of CRKP was 29.27% in Jan. 2019. The age distribution of CRKP was mainly concentrated in 21-80 years old, with the highest separation rate of 24.39% between 41-50 years old. The distribution of departments was mainly in the ICU with the separation rate of 24.39% , followed by General Surgery 21.95% , Rehabilitation Medicine 14.63% and Neurosurgery 12.20% ; the distribution of specimens was mainly sputum samples, the separation rate was 31.71% , followed by urine 19.51% , blood 19.51% and secretion 12.20% . The drug resistance rates of CRKP to imipenem and ertapenem were 90.24% and 100.00% , resp.; the drug resistance rates to ciprofloxacin and amikacin were 95.12% and 56.10% , resp. The resistance rates to β-lactamases and aminoglycosides were higher. The results of modified carbapenem inactivation method (mCIM) and EDTA modified carbapenem inactivation method (ECIM) showed that 31 strains (75.61%) were serinase phenotype, 3 strains (7.32%) were metalloenzyme; 39 strains (95.12%) were KPC type, 1 strain (2.44%) was NDM type, and 1 strain (2.44%) had both KPC type and NDM type. Only one strain (2.44%) had OmpK36 gene deletion, and the others had OmpK35 and OmpK36. There were 9 (21.95%) of 41 of OmpK35 were down-regulated, while 38 (95.00%) of 40 of OmpK36 were down regulated. Conclusion The drug resistance of CRKP is severe. The infection age was mainly young and middle-aged, and mainly concentrated in the ICU. The drug resistance mechanism of CRKP was mainly the production of KPC type serinase, and the loss and decreased expression of OmpK36.