A hybrid dynamic simulation method based on both the compartment model and the CFD model was proposed with the dual purpose of lightening the load of the process designer and of simulating reactive transport phenomena more accurately. To examine the applicability of this method, we carried out dynamic simulation of a process, in which the dynamic behavior inside the reactor was influenced remarkably by the spatial heterogeneity of state variables caused by the flow of feed. By using the hybrid simulation method, we showed that the influence of local heterogeneity in the state variables on the dynamic behavior of whole process varied with the operational conditions of mixing. Moreover, we found that it is necessary for efficient process simulation of an unsteady operation, to determine appropriately the regions to which the compartment model and CFD model could each be applied, and to develop various functions of an interface module for exchanging process data dynamically between these models.