The interaction between surface water and groundwater is crucial for the management of water resources and the preservation of ecosystems within arid basins, but knowledge on their interaction regimes at the watershed scale remains relatively limited. The present research synthesizes a range of multi-proxy data, including satellite thermal infrared remote sensing, water piezometric level, hydrochemical analyses, and isotopic signatures (2H, 18O and 222Rn), to elucidate the interaction dynamics and patterns between surface water and groundwater within a representative hyper-arid closed basin on Tibetan Plateau. The findings indicate that the water in the basin originates primarily from the glacier/snow melt water and precipitation in the mountainous regions, and would experience multiple but spatially heterogeneous interactions between river and aquifers from the mountain pass to the tail salt lakes after entering the basin. Water interaction in the piedmont alluvial plain is dominated by the pattern of river seepage into aquifers with a water flux of 25.82 m3/s, which drives the development of hierarchical groundwater flow systems in the basin. The interaction pattern converts to groundwater discharge of the local groundwater flow system at the front of alluvial fan plain, which forms the principal spring-fed rivers and the predominant overflow zone in the basin with the groundwater discharge flux of 3.22 m3/s. Most of these discharged groundwaters would infiltrate back into the aquifers in the middle-upper part of the loess plain with the river water leakage flux of 2.89 m3/s. River water and phreatic groundwater present a gradual enrichment of hydrochemcial components and water stable isotopes (2H and 18O) along the flow path due to the intense evaporation in the loess plain. The multiple water interactions between surface water and groundwater lead to the anomalous distribution of fresh water in the middle-lower stream area, which is related to the intermediate groundwater flow system and the local variable groundwater flow system. Water interaction in the lowest salt-marsh plain is in the pattern of regional groundwater flow system discharge into the tail salt lakes under natural condition, but evolves to only discharge into the artificial brine extraction canals rather than the tail salt lakes after decades of brine exploitation. Our findings provide a conceptual and preliminarily quantificational understanding of the interaction regimes between surface water and groundwater in large arid closed basins at the watershed scale.