Groundwater constitutes the dominant freshwater source in arid and semi-arid regions, yet its quality is increasingly compromised by salinization and pollution. This research elucidates the salinization and contamination of groundwater and its consequent availability for various usages, exemplified by the hyper-arid Sulengguole River watershed on northeastern Tibetan Plateau. Results show groundwaters in the downstream exhibit elevated concentrations of TH, TDS, Na+, Cl-, SO42- , and NO3 -exceeding drinking water guidelines. Groundwater hydrochemical facies are dominated by Cl-Na type (83.87 %) and mixed Cl-Mg & sdot;Ca type (16.13 %). Most of sampled groundwaters are with relatively good quality for drinking and irrigation purposes. While approximately 9.7 % are non-potable based on the EWQI assessment and about 6.5 % are irrigation-incompatible based on the entropy-weighted grey relational analysis. All poor-quality groundwater is spatially concentrated within the downstream area surrounding the Lake Jinzi. Groundwater hydrochemistry is dominantly controlled by water-rock interactions (including sulfate/silicate mineral dissolution and cation exchange) and evaporation. Notably, intensive evaporation in the lower stream area drives shallow groundwater salinization, significantly degrading both potable and agricultural usability. Concurrently, agriculturally derived NO3 -contamination further degrades drinking water quality. Sustainable groundwater utilization can be advanced through (i) enhancing fertilizer application efficiency to mitigate nitrate contamination, (ii) delineating high-quality drinking water protection zones, and (iii) planting salt-tolerant vegetation and constructing drainage ditches in high-evaporation areas to mitigate evaporative effects. This research advances fundamental understanding of groundwater chemistry formation and distribution patterns in hyper-arid watersheds, and provides scientific guidance for sustainable development, utilization, and protection of groundwater in these regions worldwide.