Optimizing the layout of intake and drainage outlets of thermal or nuclear power plans based on flow structure is of great significance to improve the operation efficiency and reduce the project investment. In this paper, a numerical model of cooling water is established in the sea area near the Haimen Cape in eastern Guangdong Province. The layout schemes of 14 separate intake and drainage outlets of four types were compared and analyzed, and the layout principles of intake and drainage outlets under similar topography and flow structure conditions were put forward. The results showed that the South-intake & North-drainage drainage scheme is a reasonable layout scheme, which accords with the coastal current of Eastern Guangdong and the tidal current movement law of Guang'ao Bay on the west side of Haimen Cape. The barrier function of the breakwater was insufficient to enable North-intake & South-drainage scheme. Other schemes were infeasible due to the short distance between the intake and outlet, and there is a “short circuit” phenomenon in the water intake.