Research purposes: The Chengdu-Guiyang Railway is one of the high-speed railways located in complicated mountain area, whose alignment traverses the transition zone from Sichuan Basin and up towards Yunnan-Guizhou Plateau, which passes across fault-fold zone in southern part of Sichuan Basin, the mountain area of northeast Yunnan and the Northwestern part of Guizhou Plateau. The major characteristics of the alignment include abundant mine reserves, several goaf zones, rich gas resources, plentiful valley areas and process of geologic structure, karst, adverse geological condition and rock salt, which indicates its complicated environmental condition. The most important part of engineering project is to avoid potential construction and operation risk by analyzing impact factors from the very beginning of the route selection phase in order to ensure the alignment technically and economically feasible. Thus, the paper mainly demonstrates the design concept of the route selection for less potential risk based on conventional design disciplines including route selection considering geology, geography, environment and major construction project conditions, which could make the geological risk controllable and even evitable, and implement the concept of integration of one county (city) and one station to create ecological engineering. Research conclusions:(1) The main factors controlling the route alignment include topography and landform, key bridge and tunnel projects, urban planning, environmentally sensitive areas, goaf areas of coal mines, karst areas, natural gas and other unhealthy geological zones. (2) The maximum slope of the line is 20‰ in general, 25‰ in difficulty and 30‰ in some cases. (3) The research results can be used for reference for railway and highway construction in complex and dangerous mountainous areas. © 2019, Editorial Department of Journal of Railway Engineering Society. All right reserved.