To implement the national strategy of "River Basin Ecological Protection" and address the synergistic threats of salinization and groundwater-derived pollution faced by the oasis groundwater systems in the arid regions of northwest China, this study takes the Manas River Basin as the research object and integrates interdisciplinary methods to reveal the synergistic risk-forming mechanisms of salinization and pollution as well as the transmission paths of health risks. Combining field sampling and laboratory analysis, the study employs the Entropy-Weighted Water Quality Index (EWQI) and health risk assessment models to analyze groundwater quality and exposure risks. It identifies natural and anthropogenically driven hydrogeochemical processes through hydrochemical evolution analysis and constructs a “salinity-pollution-risk” ternary coupling model by drawing on ideas of ecological zoning evaluation, realizing quantitative characterization and spatial zoning of multi-factor synergistic risks.The results show that the groundwater in the basin is weakly alkaline, with hydrochemical types evolving from HCO3·SO4-Ca in the south to SO4·Cl-Na in the north. The water quality in the northern oasis-desert transition zone deteriorates significantly, with over-standard rates of As, F-, and NO3- reaching 70.40%, 48.00%, and 31.20% respectively. Among them, the carcinogenic risk (CR) of As to children and adults exceeds the international thresholds by 11.4 times and 5.3 times respectively. The basin transitions from being dominated by rock weathering in the south to evaporation-concentration in the north. Salinization intensifies pollutant enrichment through evaporation-concentration and cation exchange, and combined with agricultural non-point sources and industrial emissions, forms complex pollution. The overall water quality of the basin is good, but the over-standard rate of Class Ⅲ water in the oasis-desert transition zone reaches 27.58%. Water quality deterioration is driven by both agricultural pollution and evaporation-concentration. Cl- is the main contributing factor to non-carcinogenic risks, while priority should be given to preventing and controlling children"s exposure to As-induced carcinogenic risks. TDS shows an extremely significant positive correlation with Cl- and Na+ (r=0.939, 0.840), and As concentration is highly correlated with children"s CR (r=0.825), forming a "salinity-pollution-risk" chain synergistic effect.Based on the ternary coupling model, the basin is divided into high-risk areas (18.40%, urgent treatment), medium-risk areas (27.20%, dynamic monitoring), low-risk areas (21.60%, preventive management), and safe areas (32.80%, long-term protection), with differentiated control strategies proposed. This study reveals the synergistic risk-forming laws of natural geological processes and human activities in arid region groundwater systems, providing a scientific paradigm integrating ecological zoning ideas and quantitative assessment methods for multi-element collaborative management of oasis water resources along the Belt and Road Initiative.