In order to improve the ventilation performance of main air duct in engine room of a ship, the main air duct in engine room of a container ship is taken as the research object. A diversion structure is set on the open-end plate to optimize the internal ventilation. The topological optimization concept is introduced. The stress concentration analysis of open-end plate in main air duct is conducted, the stress concentration problem of open-end plate is equivalent to that of steel plate with limited width and under tension at both ends, and the topological optimization is performed based on the Ansys Workbench software to obtain the topological optimization type open-end plate. Based on the Computational Fluid Dynamics (CFD) technology, the ventilation numerical simulations in main air duct with three types of open-end plates, namely, original type, diversion type, and topological optimization type are performed, the flow field, pressure, and flow velocity of air outlet in the main air duct are compared respectively, and the motion characteristics of air flow in the case of internal obstacles are analyzed, which can provide reference for the internal ventilation optimization of main air duct in engine room of container ship.