As a significant Cenozoic sedimentary depression in the Eastern Qaidam Basin, the Sanhu Depression hosts China’s most complete and exceptionally thick Quaternary fluvial-lacustrine clastic sedimentary sequence. To further investigate the genesis of aerial radiometric uranium anomalies and assess the uranium prospecting potential within the Quaternary strata of this region, based on the 1∶50 000 high-precision airborne radioactive survey carried out in the Sanhu Depression during 2023—2024, data processing and anomaly screening was performed. For the first time, Quaternary airborne uranium anomalies were discovered in the Fotoushan Area of the southern slope of the depression. Geological profile surveys, ground gamma-ray spectrometry, soil radon measurement, and geochemical sampling analysis were conducted on the anomalies to clarify their scale and genesis. The results show that the airborne uranium anomaly belt in the Futoushan area is located in the core and southern wing of the fold, with a length of approximately 7 km. The airborne uranium content ranges from 9 to 15.8 μg/g, and the maximum uranium content measured by ground gamma-ray spectrometry is 241.9 μg/g. The soil radon concentration in the anomaly area shows multiple high-value points (up to 386 kBq/m³). The anomalies occur in the thick-layered yellow oxidized coarse sandstones of the Qigequan Formation above the unconformity between the Shizigou Formation and Qigequan Formation, with local limonitization development. The U/Th ratio is generally 15~22, indicating strong uranium enrichment. Comprehensive studies suggest that the anomalies are caused by sandstone-type uranium mineralization. Uranium enrichment is mainly controlled by the coupling relationship between fan-delta sand bodies and low-relief fault-fold structures. The migration and accumulation of deep reducing fluids enhance the reduction capacity of Quaternary sand bodies, promoting uranium precipitation and enrichment. The Sanhu Depression has great potential for searching for large-scale Quaternary sandstone-type uranium deposits. This discovery holds significant guiding importance for the exploration of sandstone-type uranium deposits within thick Quaternary sediments in high-salinity arid basins in the northeastern margin of the Qinghai-Tibet Plateau.