Major science and technology projects enlisting and leading, as a new organizational and management approach to tackling key core technologies, is gradually becoming an important mechanism for promoting technological innovation and stimulating industrial vitality. The concept of the major science and technology projects enlisting and leading was firstly explained. Then, using the practice of Zhejiang's major science and technology projects as a typical case, the top-level design, operational models and key initiatives were reviewed. Finally, suggestions such as strengthening the top-level design in multiple dimensions are summarized and put forward from the perspective of integration and innovation, deepening the application of horse racing mode and reward mode, and mobilizing the enthusiasm of leading backbone enterprises and other diversified innovation subjects, so as to ensure the effective implementation of major science and technology projects enlisting and leading, which can provide reference for optimizing the establishment, organization and management of major scientific and technological projects and improving the efficiency of scientific research organizations.