With the increase of the installed engine power and redundancy requirements, the specification of the engine room ventilation system has been expanded, imposing difficulties on the design and layout of the engine room. A compound engine room ventilation system is introduced by combining frequency conversion fans and water-cooled internal circulating system. The CFD method is utilized to simulate a ship under several basic working conditions, optimizing the parameters of engine room fans, the layout of engine room air coolers, and the nozzle angles of jet fans. The results show that the compound engine room ventilation system effectively reduces the specification of the engine room ventilation with improved economy and flexibility. It can provide a reference for the design of engine room ventilation system for similar vessels.