The West Route of South-to-North Water Transfer Project is a strategic project to optimize the allocation of water resources and promote regional coordinated development. In order to help the scientific construction of the West Route of South-to-North Water Transfer Project and promote the construction of China’s “four horizontal and three vertical” water resources allocation pattern, this paper discusses the current situation of water resources in the northwest and the upper and middle reaches of the Yellow River, clarifies the logic of water transfer projects to promote high-quality economic, social and ecological development, studies the problems needing attention in the development of the West Route of South-to-North Water Transfer Project, and puts forward some countermeasures and suggestions, such as strengthening scientific research, establishing an ecological compensation mechanism in the water source area, doing a good job in the resettlement of religious immigrants, building a livable and industrial ecological city belt and tourism belt along the line, and accelerating the optimization and upgrading of the industrial structure in the northwest and the upper and middle reaches of the Yellow River.