Physical contact between the AgNP/Clay nanohybrid and the cellwall of bacterium is sufficient to trigger a cytotoxic signal. Throughthe plate-like clay support, highly concentrated AgNPs in eachsilicate unit may disrupt the membrane integrity on local bacterialmembrane, increase the production of intracellular ROS and inactivate the energy-dependent metabolism. The newly developedAgNP/Clay nanohybrid is proven to be highly effective for inhibitingall tested bacterial strains including MRSA. Furthermore, themechanistic understandings on the physical contact and chemicalinteractions with bacterial intracellular ROS bring up the potentialsof using this nanohybrid for the control of antibiotic-resistantbacteria.