<p>Mitochondria, as central hubs of cellular metabolism and signaling, play a pivotal role in mediating the physiological response of aquatic animals to environmental stressors, largely through their involvement in oxidative stress pathway and quality control mechanism. Understanding these molecular pathways is crucial for addressing key challenges in both aquaculture and environmental toxicology. Rather than focusing on the established fact of stress induced mitochondrial damage, this review synthesizes current knowledge to highlighting the emerging role of the mitochondrial quality control (MQC) system as a decisive determinant of stress resilience. A key research evolution is documented, showing a shift from describing oxidative stress towards exploiting MQC for adaptation and performance optimization. Furthermore, a novel theoretical framework is proposed, explaining how aquatic animals perceive and respond to environmental stress through a multi-stage process: ‘stress perception-metabolic reprogramming-quality control’. This framework not only integrates a wide range of existing research but also pinpoints key intervention points for enhancing stress resilience. Collectively, these findings provide a significant theoretical foundation and practical guidance for stress tolerance breeding in aquaculture, precise environmental management, and sustainable development.</p>