Methicillin resistant Staphylococcus aureus (MRSA) is a cause of staph infection that is difficult to treat because of resistance to many antibiotics. It has become a serious threat to global health and is associated with significant morbidity, hospital mortality and economic burden. The aim of this work is to investigate antimicrobial properties of Egyptian propolis against superbug MRSA strains and its ability to modulate some antibiotic resistance. Propolis consists of a complex mixture of resinous substances collected by honeybees . A total of 130 Staphylococcus aureus clinical isolates were recovered from patients in Beni-Suef University hospital. It was found 79.23% (103/130) cefoxitin resistant Staphylococcus aureus (MRSA) and further confirmed as being positive for mec A gene. All isolates have been tested for sensitivity against nine antibiotics. About 46% of isolates were multi-drug resistant to at least 6 of the tested antibiotics. All isolates were Linezolid and vancomycin sensitive. Broth microdilution method was used to determine antimicrobial activity of ethanolic extract of propolis (EEP). MIC values of EEP were ranged from 0.195 to 1.565 mg/ml, while its MBC were varied between 0.781 to 3.125 mg/ml. By Time Kill assay, EEP shows a potential decrease in MRSA viable count within 4 hours of incubation with total clearance after six hours of contact. The in-vitro propolis trial against MRSA presented high synergistic activity when combined with Amikacin and Gentamycin, Clindamycin, vancomycin, Linezolid and moderate synergism with ciprofloxacin. Conclusion. Propolis as a natural product may help in modulating MRSA multidrug resistance.