Background: Klebsiella pneumoniae causes any types of hospital-acquired infections (HAIs). Resistance to quinolone antibiotics increased rapidly in K. pneumoniae. Objectives: This study was designed to investigate the prevalence of quinolone resistance, detection of plasmid mediated (qnrA and qnrS) genes in K. pneumoniae causing hospital-acquired infections (HAIs) in ICUs of Mansoura Emergency Hospital. Additionally, determination of risk factors for quinolone resistance. Methodology: K. pneumoniae isolates were collected from different samples of patients admitted to Mansoura Emergency Hospital and presented with different infections. K. pneumoniae isolation and identification was performed by biochemical reactions. K. pneumoniae quinolone susceptibility was identified by disc diffusion method. The qnrA and qnrS were detected by PCR. Results: A total of 65 K. pneumoniae isolates were recovered in the studied ICUs patients̓ samples. The highest resistance of K. pneumoniae isolates was to ciprofloxacin and ceftriaxone (80% and 70%, respectively). The qnrS gene was detected in 28 cases, and qnrA was detected in 2 cases. Regarding risk factors for resistance, male sex (OR=4. 9, P: 0.016), diabetes (OR: 6.9, P: 0.073) and hospital stay more than 8 days (OR: 1.99, P 0.002) were significantly associated with quinolone resistant K. pneumoniae. Conclusion: High rates of resistance were detected in K. pneumoniae to many classes of antibiotics. Quinolone resistant was reported among the highest one. Presence of quinolone resistance genes qnrA & qnrS could be considered among the main causes of this resistance. Diabetes mellitus, hypertension and increased hospital stay are significant risk factors for development of this resistance.