In order to find a safe and effective control method of Shigella flexneri， the study investigated the inhibitory effect of protocatechuicaldehyde （PC） against S. flexneri and its possible mechanism. The minimum inhibitory concentration （MIC）， the minimum bactericidal concentration （MBC） of PC against S. flexneri were determined. Besides， cell morphology potential， the changes of intracellular ATP concentration， membrane potential， the effects on synthesis and destruction of protein as well as the growth curve were also measured to investigate the possible antimicrobial mechanism of PC against S. flexneri. The results showed that the MIC of PC against S. flexneri was 0.5 mg/mL and the MBC was 4.0 mg/mL. Field emission scanning electron microscopy showed that the morphology of S. flexneri was damaged， while PC treated cells were wrinkled and shriveled. In addition， PC affected the cell membrane permeability of S. flexneri， with mass concentration of 2×MIC and 4×MIC reduced the intracellular ATP concentration， cells treated with PC showed hyperpolarized cell membranes. It also destroyed cell proteins and inhibits cell protein synthesis. Moreover， after treatment with PC， the growth retardation period of S. flexneri was prolonged and the specific growth rate was reduced. In conclusion， PC has good antimicrobial activity against S. flexneri， it has the potential to be used in food industry as a natural and safe bacteriostatic substance.