As an important inland river in the Hotan region, the Yurungkash River holds strategic significance for regional sustainable development and ecological security. This study analyzes the contradiction between water supply and demand in the basin and its intensifying trend. The results indicate that although recent runoff has shown an increasing trend due to glacial melt, the natural endowment of “abundance in summer and scarcity in winter,” coupled with insufficient regulatory capacity of water conservancy projects, leads to prominent spatiotemporal unevenness. On the demand side, structural imbalances are evident, with agricultural water use accounting for over 90%, and inefficient water use severely encroaches on ecological and domestic water supplies, resulting in the degradation of downstream green corridors and groundwater over-extraction. It is projected that by 2030, the supply–demand gap in dry years will reach 155 million m3. The study proposes a four-pronged regulatory strategy system centered on “water conservation priority,” encompassing “conservation-development-management-optimization.” This system includes comprehensive measures such as agricultural water efficiency, construction of water conservancy hubs, improvement of water rights markets, and implementation of ecological flood pulse management, providing a decision-making basis for ensuring water security in the basin.