At present, most intercepting facilities in water intake open channel of nuclear power plant are passive. Moreover, the correlation between the layout of intercepting facilities and hydraulic conditions of water intake open channel is not considered. Hence, the layout of intercepting facilities is unreasonable. The cooling water intake system of nuclear power plants faces risks. In this paper, The flow field characteristics of water intake open channel under typical sea hydrologic conditions were studied. Then, the migration path and aggregation rule of floating or suspended objects are simulated along with the flow. The blockages-removal effect of floats and marine organisms are studied after different intercepting engineering measures are carried out in water intake open channel. The technical route combining mathematical model and physical model test is adopted. Finally, the principle and scheme of the interception engineering layout of active intercepting and guiding are proposed. The optimized interception engineering layout can effectively guide suspended or floating blockages to the outside of water intake, or guide blockages in water intake open channel to the area without disaster risks, where the blockages are also easy to be salvaged. It can significantly reduce the large quantity of blockages into the cooling water intake system, which will also reduce the blockage loads for all intercepting facilities. Thereby, the defense capability of nuclear power plant cold source system against potential water intake blockages is greatly improved.