The extract of Cladonia stellaris has good in vitro antimicrobial activity.To clarify its antibacterial molecular mechanism,this study used methicillin-resistant Staphylococcus aureus (MRSA) as the indicator bacterium.Metabolomics were used to obtain the changes in intracellular differential metabolites of MRSA treated with C. stellaris,and molecular docking was used to verify the affinity of differential metabolites with relevant proteins and antibacterial components of C. stellaris,analyzing the antibacterial mechanism of C. stellaris.In vitro antibacterial experiments showed that the methanol extract of C. stellaris  had a broad antibacterial spectrum and was highly sensitive to MRSA.Metabolomics and molecular docking results indicated that C. stellaris acted on four potential different antibacterial targets:histidine kinase,penicillin-binding protein PBP2A,quinolone resistance protein NorA and S-adenosylmethionine synthetase,enhancing adhesion to MRSA cell membrane and inhibiting the action of efflux pump NorA,interfering with histidine and methionine metabolism to exert antibacterial effects.This study provides a basis for exploring the molecular mechanism of C. stellaris against MRSA.