Redox imbalance induced by the accumulation of reactive oxygen species (ROS) accelerates age-related processes, often accompanied by a decrease in circadian rhythm amplitude. However, the underlying mechanisms by which ROS modulate circadian rhythms remain poorly understood. In this study, we found that ROS disrupt circadian rhythms in both zebrafish, as indicated by changes in diurnal behavior and clock gene expression, and in a human cell model. Using weighted gene co-expression network analysis (WGCNA) and machine learning approaches (RF, LASSO, SVM), EZH2 was identified as a key gene involved in regulating circadian rhythms under oxidative stress conditions. To further investigate the role of EZH2, we employed ezh2