Abstract:[Background] Cronobacter sakazakii is an opportunistic pathogen transmitted by food, which affects mainly newborns, infants and immune compromised adults, with reported case fatality rates of 50%?80%. [Objective] The aim of this work was to investigate the antimicrobial effect of a natural plant-derived compound protocatechuic acid (PCA), and its effects on cell membrane permeability of C. sakazakii strains. [Methods] We determined the Minimum Inhibitory Concentrations (MICs) using agar dilution method, and growth curves were also measured. Changes in intracellular pH, membrane potential, intracellular ATP concentration, membrane integrity and cell morphology were measured to elucidate the cell membrane damage induced by PCA. [Results] The experimental results indicated that the MICs of PCA against C. sakazakii strains were 2.5?5.0 mg/mL. PCA decreased growth rate of C. sakazakii and increased the cell membrane permeability of cells, as evidenced by reduction of pHin, occurrence of cell membrane hyperpolarization/depolarization, intracellular ATP concentration decrease, reduction of membrane integrity and changes of cellular morphology in C. sakazakii cells after exposure to PCA. [Conclusion] These findings demonstrated that PCA had antimicrobial activity against C. sakazakii. It exerted antimicrobial action partly through causing cell membrane dysfunction and changes in cellular morphology. Considering its antimicrobial properties, together with its well-known nutritional functions, PCA has potential to be developed as a supplement in infant formula or other foods.