Background & Aims: The efflux pumps play an important role in the development of drug resistance in Klebsiella pneumoniae. The aim of this study was to investigate the antibiotic resistance, and the presence of efflux genes, as well as molecular typing in clinical isolates of Klebsiella pneumoniae. Materials & Methods: In this cross sectional descriptive study, a total of 100 K. pneumoniae isolates were collected from Milad hospital, Tehran, Iran. Bacterial identification was carried out by biochemical tests and antimicrobial susceptibility testing performed according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. The presence of TolC, AcrAB, MdtK genes were investigated using polymerase chain reaction (PCR) and molecular typing was performed according to the enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR). Results: The results showed that 48% of isolates were multidrug resistant (MDR). The highest rate of resistance was observed against amikacin (65%) and the lowest resistance was found in aztreonam and fosfomycin (1%). The occurrence of AcrAB gene (96%) was the highest, followed by mdtK (82%) and tolC (79%). ERIC-PCR revealed 16 different genotypes among K. pneumoniae isolates. There was a significant association between ERIC-PCR pattern and efflux pump genes in some clonal types (p<0. 05). Conclusion: Our findings indicated the high prevalence of multidrug resistance and efflux genes in Klebsiella pneumoniae isolates. The strategy for suppressing these efflux systems may be useful in the treatment and control of the multidrug-resistant Klebsiella pneumoniae.