B-cells serve as a niche for Salmonella to establish a chronic infection, enabling bacteria to evade immune responses. One mechanism Salmonella uses to survive inside B-cells involves inhibiting the NLRC4 inflammasome activation, thereby preventing pyroptotic cell death. This study investigates whether Salmonella-infected B-cells can mount bactericidal responses to control intracellular bacteria. Our results show that Salmonella-infected B-cells can produce and release TNFα, IL-6, and IL-10, but not RANTES. Furthermore, priming B-cells with TNFα, IL-1β, or IFNγ enhances their bactericidal activity by promoting the production of reactive oxygen and nitrogen production species, reducing intracellular load. These results suggest that B-cells can clear Salmonella infection within a pro-inflammatory environment. However, the concurrent production of IL-10 may counteract the effects of pro-inflammatory cytokines, potentially modulating the immune response in the microenvironment.