Oxygen reduction reaction (ORR) is critical cathodic process in energy conversion devices such as proton exchange membrane fuel cells (PEMFCs). Its sluggish kinetics severely limit the efficiency and commercialization prospects. However, catalysts design strategies based on the static initial structures often fail to adequately capture the genuine working state and reaction mechanisms under realistic electrochemical conditions. Here we systematically outline recent significant progress in elucidating the ORR process through dynamic theoretical simulations and in-situ characterization. The role of dynamic simulations (electrolyte environment, applied potential, pH dependence, and ions effects) in understanding the evolution of catalyst structures and reaction processes under practical conditions was discussed. Meanwhile, the applications of in-situ X-ray absorption spectroscopy (XAS), vibrational spectroscopy (Raman spectroscopy, Fourier transform infrared spectroscopy), and microscopic in the evolution of catalyst electronic states and the behavior of reaction intermediates during the ORR process were summarized. Through the mutual validation of theory and experiment, we clarify the decisive regulatory role of the dynamic interfacial microenvironment on activity. Finally, based on dynamic research, the rational design principles and future research directions of electrocatalysts for actual reaction conditions were prospected.