Abstract:Major original innovation needs to rely on interdisciplinary and deep pioneering research to expand the boundaries of human knowledge. National Research Institutes, as an important national strategic scientific and technological force, bear responsibility and national mission in accelerating the creation of original innovation source, accelerating the breakthrough of key core technologies, and striving to seize the commanding heights of science and technology.In this study, through in-depth analysis of the forwardlooking strategic positioning, clear top-level design, and efficient research mechanism and organization mode in the New Generation Lithography system breakthrough project, which was organized by the National Laboratory of the United States in the 1990s, we further provide insights for the national strategic scientific and technological force to efficiently promote the major original innovation in China, and to facilitate the major original innovation integration breakthrough of new scientific discovery, new technological trajectory and new industrial direction at the strategic frontier.