Host selective toxins (HSTs) are small molecule phytotoxins that control the pathogenicity of microbes in the host plant, but the mechanistic basis for their selectivity is unknown. We developed AcIle-EDA (Aclle-(+)-9,10-epoxy-8-hydroxy-9-methyldeca-trienoic acid) as a molecular probe of an HST, examined its mode of action in genetically modified Oryza sativa, and found it to trigger ROS production through NADPH-oxidase OsRBOHB, causing the emergence of pathogenic traits. This result strongly suggests that AcIle-EDA functions through the hijacking of the plant-microbe interaction system.