Abstract: | The formation of bacterial biofilm is one of the causes of antimicrobial resistance, often leading to persistent infections and a high fatality rate. Therefore, there is an urgent need to develop novel and effective strategies to inhibit biofilm formation. Adenosine triphosphate (ATP) plays an important role in bacterial adhesion and biofilm formation through stimulating cell lysis and extracellular DNA (eDNA) release. Herein, a simple and robust strategy for inhibiting biofilm formation is developed using CeO2‐decorated porphyrin‐based metal‐organic frameworks (MOFs). The function of extracellular ATP (eATP) can be inhibited by CeO2 nanoparticles, leading to the disruption of the initial adhesion of bacteria. Furthermore, planktonic bacteria can be killed by cytotoxic reactive oxygen species (ROS) generated by MOFs. As a consequence, the synergic effect of eATP deprivation and ROS generation presents excellent capacity to prevent biofilm formation, which may provide a new direction for designing flexible and effective biofilm‐inhibiting systems. |