This study was conducted to acknowledge microbiological and clinical characteristics of hospital-acquired pneumonia (HAP) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). A retrospective, 1:1 matched (age, gender, specimen source, and ward) case-control study was conducted during 2015-2017 in a tertiary teaching hospital in Anhui, China. Multivariate logistic regression analysis demonstrated that prior central venous catheter use, sputum suction, continuous renal replacement therapy, and exposure to fluroquinolones were independent risk factors for the morbidity of CRKP infection for HAP. Treatment failure for infection was an independent risk factor for crude in-hospital mortality, while the use of fluroquinolones may improve the effective treatment for infection (p = 0.040). Among 74 CRKP strains, 85.1% of them were positive for the production of KPC-2, and one of them was detected for co-harboring blaKPC-2 and blaIMP-38-like. Separately, sequence type (ST) 11 (81.1%) was the predominant ST in this study, and ST11 CRKP isolates were related with higher detection rate of blaKPC-2 and lower resistance rate to trimethoprim/sulfamethoxazole when compared with non-ST11 ones. Moreover, resistance to carbapenem was associated with higher mortality (35.1%) and hospitalization costs for HAP patients with K. pneumoniae infection. Invasive procedures may increase the morbidity of CRKP infection for HAP. Prior exposure to fluroquinolones is associated with the development of resistance, but as a targeted treatment it may be effective.