Klebsiella pneumoniae (K. pneumoniae) is an important pathogen associated with various infections. The emergence of antibiotic resistances, such as quinolone resistance and those due to extended-spectrum beta-lactamases (ESBL), reduces the available choices for treatment. The objectives of the current study include the evaluation of the prevalence of the plasmid-mediated quinolone resistance genes qepA, acrA, acrB, and aac(6’)-Ib-cr by polymerase chain reaction (PCR) in K. pneumoniae and the determination of the mechanism relating these genes to the ESBL phenotype and resistance to other groups of antibiotics. In total, 300 clinical isolates of K. pneumoniae were included in the study. Isolates were subjected to antibiotic sensitivity tests using the disc diffusion method. Quinolone resistance by the minimum inhibitory concentration method and detection of ESBL resistance by the double disc diffusion method were also determined. PCR analyses revealed the prevalence of acrA, aac(6’)-Ib-cr, acrB, and qepA in 74.3%, 73.7%, 71%, and 6.7% of the isolates, respectively. Quinolone-resistant isolates positive for plasmid-encoded genes represented 82.7% of K. pneumoniae isolates positive for ESBL activity. The results also showed that the isolates of K. pneumoniae carrying plasmid-encoded quinolone resistance genes had significantly increased resistance to amikacin, amoxicillin/clavulanate, gentamicin, and cefoxitin than those isolates without quinolone resistance genes. Therefore, there was a high prevalence of acrA, acrB, and aac(6’)-Ib-cr among K. pneumoniae and the prevalence of quinolone resistance was significantly associated with the ESBL resistance phenotype. Moreover, the presence of quinolone resistance genes was associated with resistance to aminoglycosides, namely amikacin and gentamicin.