The cooling water intake system of coastal nuclear power plant involves multiple parts from the sea to the land. Moreover, the interception facilities of cooling water intake system are technically complex and face variable blocking risks. In order to improve the safety, stability and economy of nuclear power, for the first time, a systematic study on prevention and control measures to blockages of cooling water intake system in coastal nuclear power plant is carried out from the systematic perspective. The principle of active defense, depth setting, stepped filtration and permanent or temporary combination are adopted in this study. The research contents concern system design, equipment selection and technology layout, etc. Some key technologies, such as cold source blockages investigation, flow field active guidance and avoidance, cascade filtering system, pump station design, monitoring and early warning system, emergency response, etc., have been emphatically studied and optimized. As a result, a reasonable and systematic scheme of prevention and control measures to blockages of cooling water intake system is proposed. The application of this systematic scheme will enable nuclear power plant to form a strong-matrix prevention and control model containing all parts of the cooling water intake system. It can improve the active defense capability of cooling water intake system against blockages and reduce the occurrence of cooling water intake blockage incidents in nuclear power plant.