Abstract: The Sichuan-Tibet Railway is a century project under construction. The complex geological evolution history has led to large differences in geo-environmental conditions along the railway. Hydrogeological, engineering geological, and environmental geological problems are complex and changeable, which deserves great attention in engineering construction and future operations. Based on a brief review of the past geological work on the Sichuan-Tibet Railway corridor, the hydro-engineering-environmental geological problems that may be faced during the railway construction have been described. The hydrogeological problems include 1) high-pressure water inrush from plateau tectonic karst, 2) high-pressure water inrush and mud outburst from faulted bedrock fissures, 3) high-temperature hot water thermal damage. The engineering geological problems include 1) active faults and strong earthquake disasters, 2) high in-situ stress and rock burst or large deformation in deep tunnel, 3) problem rocks or soils and their disaster effects, 4) high-position landslide disaster chain. The environmental geological problems include 1) acidic water corrosiveness from coal-bearing strata and hydrothermal deposits, 2) wetland ecological degradation, 3) interaction effects between the railway construction and the sensitive ecological environment. In the meanwhile, key scientific and technological issues, which should be deeply studied in the future, are put forward. In terms of hydrogeology, such as 1) sequence law of plateau karst development and types of tectonic karst water storage structures, 2) disaster-generating models and prediction methods of water and mud bursts in deep-buried tunnels, 3) active fault control mechanisms and geothermal water circulation models, 4) identification of high-temperature heat hazard risk and geothermal resources utilization technology. In terms of engineering geology and geohazard, such as 1) investigation of fine features of active faults and related engineering fault effects, 2) development features of deep tectonic stress fields in complex geological structures, 3) engineering geological properties of tectonic mélange belts and related disaster effects, 4) surrounding rock stability and disaster effects of deep-buried tunnel under water-mechanical-thermal multi-field coupling condition, 5) mechanisms of high-position run-out landslide and risk control technology under internal and external dynamic coupling. In terms of environmental geology, such as 1) mechanisms of plateau multi-source water conversion cycle and the technology of ecological water demand control in the ecologically fragile area, 2) hydro-ecological environmental effect of tunnel construction, 3) key technology of ecological geological environment monitoring, evaluation and protection, 4) geo-ecological environmental effect of global climate warming, etc. From the view of combining non-profit geological surveys and commercial engineering surveys, a response strategy has been proposed that geological surveys are the foundation, scientific and technological research is the key, and the monitoring of potential hazards and engineering control should be promoted, which provides suggestions on developing direction for hydro-engineering-environmental geology work on major project planning areas.