Deepening the reform of the science and technology system is the key to building a world power in science and technology. Since the 18th CPC National Congress, the reform of China’s science and technology system has achieved remarkable results. In the face of the new requirements of realizing a high level of scientific and technological self-reliance and self-improvement, it is necessary to carry out reform of the scientific and technological system in terms of macro-strategic support, meso-resource allocation and micro-incentive mechanism. At present, the overall effectiveness of China’s innovation system is not high, there are irrational allocation of scientific and technological resources, major scientific and technological project management system is inconsistent with the law of scientific research, strategic scientific and technological forces, such as the mechanism of synergy is not sound and other persistent problems and challenges. On the basis of in-depth analysis of the reasons, it is proposed to reshape the science and technology governance system with “demand orientation”, to improve the new national system and to strengthen the main body of enterprise science and technology innovation to enhance the effectiveness of the innovation system, and to enhance the efficiency of the innovation system with “demand orientation”. We should reshape the S&T governance system with “demand orientation”, improve the effectiveness of the innovation system with “perfecting a new type of national system” and “strengthening the main body of enterprises in S&T innovation”, and promote the transformation of the S&T management function with the “four new grasps”. Specific measures include improving the working mechanism of the Central Science and Technology Commission, optimizing the management of major science and technology projects, coordinating scientific and technological inputs, optimizing the management mechanism of basic research, promoting the systematic synergy of strategic scientific and technological forces, and strengthening the status of enterprises as the main body of scientific and technological innovation.