As the third-generation nuclear power technology with independent intellectual property rights in China, HPR1000 meets the world’s highest safety requirements and the latest technical standards, occupying a pivotal position in the field of nuclear energy. HPR1000 adopts advanced design concepts such as advanced core technology and a safety system that combines active and passive features. The total number of HPR1000 units in operation and under construction at home and abroad has reached 33, making it the third-generation nuclear power technology with the largest number of units in operation and under construction globally. Moreover, the units already in operation are running smoothly. With the increase in its operation time, conducting Periodic Safety Reviews (PSR) is of great significance for ensuring long-term safe and reliable operation. This paper intends to formulate the application strategies of PSR based on the design basis and regulatory standards of HPR1000, through researching the key points and review methods of each factor of PSR. The aim is to make an objective and comprehensive evaluation of the actual status of HPR1000 nuclear power plants in operation, implement rectification tracking actions and experience feedback, so as to maintain the healthy status of the nuclear power plants in operation and achieve continuous improvement. The research results of this study are crucial for the long-term safe and stable operation of HPR1000. In the future, challenges such as unit aging still need to be addressed to further improve the strategies of PSR.