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<i>Salmonella</i> genus represents the most common foodborne pathogens causing morbidity, mortality, and burden of disease in all regions of the world. The introduction of antimicrobial agents and <i>Salmonella</i>-specific phages has been considered as an effective intervention strategy to reduce <i>Salmonella</i> contamination. However, data from the United States, European countries, and low- and middle-income countries indicate that <i>Salmonella</i> cases are still a commonly encountered cause of bacterial foodborne diseases globally. The control programs have not been successful and even led to the emergence of some multidrug-resistant <i>Salmonella</i> strains. It is known that the host immune system is able to effectively prevent microbial invasion and eliminate microorganisms. However, <i>Salmonella</i> has evolved mechanisms of resisting host physical barriers and inhibiting subsequent activation of immune response through their virulence factors. There has been a high interest in understanding how <i>Salmonella</i> interacts with the host. Therefore, in the present review, we characterize the functions of <i>Salmonella</i> virulence genes and particularly focus on the mechanisms of immune escape in light of evidence from the emerging mainstream literature.