Listeria monocytogenes is one of the foodborne pathogens (FBP), which are a threat to the consumers' health, able to cause listeriosis. L. monoytgenes cells, which can easily adapt and survive stresses, can develop resistance to antibiotics used in standard therapy. Phenolic acids that are a natural defense mechanism against stress conditions in plants, might be used as an antibacterial-candidate in foodborne diseases, so there is a need for a better understanding of the stress-induced responses and mechanisms of bacteria against these substances. Proteomic approaches are an invaluable method for identifying the stress response in pathogenic bacteria. For this purpose, in this study firstly, the antibacterial effects of two phenolic acids (3-HPAA and 4-HBA) on bacteria were investigated by determining the minimum inhibitory concentrations (MIC). Subsequently, target changes in the protein profile due to antimicrobial effects of phenolic acids were evaluated using a soft ionization technology and mass spectrometry-based comparative gel-free proteomic approach (Shotgun proteomics). According to the results, Listeria monocytogenes could not develop resistance to both phenolic acids. This study emphasizes the importance of using of phenolic acids as a novel and natural therapy methods to overcome antibiotic-resistant pathogenic bacteria.