The methicillin-resistant Staphylococcus aureus (MRSA) is one of the most frequent nosocomial pathogens in developed countries. Among the Gram positive bacteria, S.aureus is responsible for a large number of deaths worldwide. MRSA is resistant to a variety of antibiotics including tetracyclines, aminoglycosides and fluoroquinolones. Studies found that NorA is a predominant protein efflux pump responsible for efflux mechanisms in S.aureus (Sabatini et al., 2012). For these reasons, NorA has been one of the most studied Gram-positive bacterial efflux pumps in the search for efflux pump inhibitors. Although other protein targets have been investigated and there are some newly found derivatives proved to have inhibitory activities towards those proteins, there is still a lack of QSAR studies focused on such inhibitors. With respect to NorA in S.aureus, while there have been a number of natural and synthetic product known to be inhibitors of NorA efflux pump, there is still a need to discover new and potent NorA inhibitors. However, the slow emergence of high-resolution structure of this pump has hampered the intelligent design of its modulators, necessitating a ligand-based approach. With currently available structural data regarding known NorA inhibitors, robust QSAR models were generated, paving the way for preliminary identification of compounds with NorA inhibitory activities, whereby more thorough research can be conducted in order to identify the inhibitors with high potentiality to become future “adjuvants” of antibiotics.