Bacterial fruit blotch is one of the most destructing diseases of melon producing-regions. Here, zinc oxide quantum dots (ZnO QDs) were synthesized, and their antibacterial activity against Acidovorax citrulli was investigated. The results indicated that the obtained ZnO QDs displayed 5.7-fold higher antibacterial activity than a commercial Zn-based bactericide (zinc thiazole). Interestingly, the antibacterial activity of ZnO QDs irradiated with light was 1.8 times higher than that of the dark-treated group. It was because ZnO QDs could induce the generation of hydroxyl radicals and then up-regulate the expression of oxidative stressrelated genes, finally leading to the loss of cell membrane integrity. A pot experiment demonstrated that foliar application of ZnO QDs significantly reduced the bacterial fruit blotch disease incidence (32.0%). Furthermore, the supply of ZnO QDs could improve the growth of infected melon seedlings by activating the antioxidant defense system. This work provides a promising light-activated quantum-bactericide for the management of pathogenic bacterial infections in melon crop protection.