Proton exchange membrane water electrolyzer (PEMWE) is crucial for the storage and conversion of renewable energy. However, the harsh anode environment and the oxygen evolution reaction (OER), which involves a four-electron transfer, result in a significant overpotential that limits the overall efficiency of hydrogen production. Identifying active sites in the OER is crucial for understanding the reaction mechanism and guiding the development of novel electrocatalysts with high activity, costeffectiveness, and durability. Herein, we summarize the widely accepted OER mechanism in acidic media, in situ characterization and monitoring of active sites during the reaction, and provide a general understanding of the active sites on various catalysts in the OER, including Ir-based metals, Ir-based oxides, carbon/oxide-supported Ir, Ir-based perovskite oxides, and Ir-based pyrochlore oxides. For each type of electrocatalysts, reaction pathways and actual active sites are proposed based on in situ characterization techniques and theoretical calculations. Finally, the challenges and strategic research directions associated with the design of highly efficient Ir-based electrocatalysts are discussed, offering new insights for the further scientific advancement and practical application of acidic OER. (c) 2025 Science Press and Dalian Institute of Chemical Physics, Chinese Academy of Sciences. Published by Elsevier B.V. and Science Press. All rights are reserved, including those for text and data mining, AI training, and similar technologies.