Oxidative damages lead to accumulated harmful wastes, which in turn aggravate the related diseases and ROS imbalance. Therefore, provoking the defense system against severe oxidation and maintaining ROS homeostasis are desired. Herein, we used a mitochondria-targeted aggregation-induced emission luminogen (AIEgen) as a phototherapy agent for neuron protection by virtue of its efficient ROS generation in aggregates and mitochondrial delivery. It is demonstrated that controllable ROS generation within mitochondria can trigger defensive autophagy against oxidative damages in neuron cells. This work not only verifies the concept that taming ROS can be used for cell protection, but also provides a promising method to trigger autophagy against destructive oxidation, displaying broad prospects for alleviating oxidation-related diseases and promoting cell-based therapy.