Some bacterial pathogens invade and persist inside host cells, where they are protected from antimicrobial agents and immune responses. Staphylococcus aureus, a difficult-to-treat pathogen due to its resistance to antibiotic therapy, can thrive intracellularly, exploiting host cell nutrients and causing long-term colonization and recurring infections. Effective therapies that target intracellular pathogens are urgently needed. In this study, Ge et al. developed cells that mimic the innate immune activity elicited by natural killer (NK) cells to clear intracellular S. aureus infections. These NK cell mimics are composed of modified inorganic mesoporous silica nanoparticles that are activated by the redox conditions surrounding infected cells. Once activated, these carriers release perforins that perforate the cell membrane of infected cells, creating channels through which granzyme B, the other component present in the nanoparticle, diffuses through and kills the intracellular pathogens. Treatment with NK cell mimics eliminated S. aureus in vitro and in vivo, and boosted both the innate and adaptive immune responses in the host. Whether this strategy could be effective against other intracellular pathogens remains to be determined.