In view of the situation that large amounts of marine sewage and organisms enter into the cooling water intake system of a coastal NPP at BeiBu-bay, China, which affects the safe and stable operation of NPP, the optimization research on blockage prevention in the water intake engineering is carried out. Based on the statistical analysis of a large number of NPPs’ cooling water source safety incidents globally, the hydraulic characteristics of shell debris in water-intake open channel are studied first, and the source of shell debris in the drum filter at the water intake pump room is analyzed. Secondly, the water intake layout project scheme is optimized through the wave model test, which can effectively improve the wave cover in the water intake channel. At last, through the wave physical model test, the overall force of the network is studied under the combined action of wind, wave, flow and sewage, and the anchoring foundation which can guarantee the stable operation of the trash-intercepting network is optimized. By carrying out the optimization design of water intake engineering, reducing the waves in channel, reducing the possibility of marine sewage and organisms entering the channel, adding the trash-intercepting network facilities and forming effective cover. It can not only effectively avoid or reduce the impact of marine sewage and organisms on the cooling water source safety of NPPs, but also minimize the loss of marine organisms during the operation of NPPs.