Objectives: To investigate photodynamic technology (PDT) inactivation of Grimontia hollisae (Gh) and Vibrio alginolyticus (Va) mediated by water soluble curcumin and its mechanism. Methods: The inactivation effect of Gh and Va by PDT was determined by colony counting method， reactive oxygen species (ROS) production in bacteria was tested by ROS assay kit， total protein degradation was analysed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and virulence gene damage was examined by agarose gel electrophoresis. Results: Water soluble curcumin PDT significantly inactivated Gh and Va. The inactivation effects increased with dark incubation time， illumination time and curcumin concentration. After PDT treatment， Gh and Va decreased by 7.98 lg (CFU/mL) and 7.80 lg (CFU/mL)， and the inactivation rate was over 99.99%. PDT promoted the ROS level in bacteria to degrade bacteria protein and DNA， but no significant damage to virulence genes of Gh and Va was observed. Conclusion: Curcumin PDT can effectively inactivate Gh and Va via ROS and shows potential application in aquatic food safety.