The state key laboratory is not only an important platform for scientific and technological innovation in China, but also a part of the innovation system. It is of unparalleled significance in promoting discipline development, gestating major scientific research achievements, cultivating scientific and technological leaders, undertaking major projects and carrying out international and domestic cooperation. In the face of the need for development and reform under the new situation, the relevant work of state key laboratories in operation management, evaluation and assessment also needs to make further improvement and progress. In this paper, we take the State Key Laboratories as the research object, organize the development history, discuss the relevant methods and roles of management and assessment mechanism, and propose improvement suggestions for the management and assessment mechanism of State Key Laboratories under the new situation. It can also provide some reference for the long-term development and reform operation of the state’s key laboratories and other laboratories. The evaluation work of state key laboratories should strengthen the combination of qualitative and quantitative mechanisms, optimize evaluation grouping, expert selection and evaluation index system, keep pace with the times, comprehensively and objectively reflect the basic situation and scientific research level of state key laboratories, and provide guidance and reference for national strategic deployment and laboratory innovation development. The State Key Laboratory shall give full play to its disciplinary advantages and the backbone of scientific and technological innovation, achieve breakthroughs and innovations in strategically contested fields, cutting-edge technologies, and “stuck neck” technologies, and promote China’s dominance in the battlefield of the world’s science and technology game.