Overcoming resistance to Methicillin resistant Staphylococcus aureus (MRSA) is attainable by inhibition of penicillin-binding protein (PBP-2a). Nowadays, natural products are used to enhance the therapeutic potential of drugs. Naringenin, a bioactive flavonoid exhibits potential antibacterial activity. Hence, present study demonstrates it’s potential alone and in combination with β-lactam antibiotics against MRSA. Individual Minimum inhibitory concentration (MIC) of Naringenin and selected antibiotics was determined by agar dilution method in 7clinical isolates. The anti-bacterial potential of naringenin in combination with the β-lactam drugs was evaluated using checkerboard method and FIC-index was calculated. Effect of naringenin on the expression of PBP-2a was studied using immunoblotting. MIC of naringenin against MRSA was 125μg/ml. On combination of naringenin with oxacillin and cloxacillin, 5 and 4 strains showed synergistic effect respectively. All the strains showed indifference effect when naringenin was treated with amoxycillin. Hence, it was found that the susceptibility of MRSA positive strains was augmented in the presence of naringenin. Combination of different drugs with naringenin showed suppression of PBP-2a protein. It is found that combination of naringenin and β-lactam antibiotics intensified the antibacterial property of these drugs. The present study also demonstrates that the mechanism of action of naringenin is dependent on the inhibition of PBP-2a.