Klebsiella pneumonia (KP) is a common pathogenic bacteria which can cause infections to the respiratory tract, gastrointestinal tract and urinary tract. The infections usually break out in the neonatal ward, urological ward and tutelary ward. Multi-drug resistant KP strain bring great difficulty to the clinical antibiotic treatment. The present paper mainly discuss the drug resistance mechanism of KP in five aspects including KP β lactam resistance mechanism, the lack of outer membrane protein and the change of the target position, drug resistance mechanism associated with biofilm, drug resistance effects of efflux pump and in tegron. By roundly understanding of the drug resistance mechanism of KP, the rational use of antimicrobial agents and efficient prevention of drug-resistant bacteria may be achieved.