Abstract: For the in-situ recovery (ISR) mining of sandstone-type uranium deposits with the high total dissolved solids (TDS), the desalination process of injecting fresh water was required. In the past, the main research was to reduce the TDS of groundwater to prevent the influence of calcium sulfate and calcium carbonate precipitation from clogging pores. However, the influence mechanism of the desalination process on the precipitation and plugging of calcium sulfate and calcium carbonate from the ion sources of SO^2-₄, Ca²⁺ and CO^2-₃ in groundwater was not discussed. To explore the water-rock reaction between the leaching ore body and the injected fresh water in ISR desalination process of Shihongtan sandstone uranium mine in Xinjiang (China), the hydrochemical characteristics of the pregnant solution were analyzed by soaking the ore with distilled water. The results show that the pregnant solution was weakly alkaline, and the hydrochemical type was Cl-SO₄-Na type, and the TDS was about 1.27 g/L higher than that of the leaching agent. The water-rock reaction mechanism in the desalination process was analyzed by inversion simulation. The results show that the minerals are mainly dissolved in halite, followed by sulfate and carbonate, while silicate is the least dissolved in the soaking process. It shows that the mineral dissolution will release a large number of soluble ions in the desalination process, which will hinder the desalination of groundwater. In addition, evaporative salt rock is the main influence mineral. The desalination process mainly occurs in the dissolution of dolomite, feldspar, gypsum, halite and hematite, and the precipitation of muscovite and calcite. Kaolinite, Ca-montmorillonite and illite in clay have the possibility of dissolution, and the precipitation is mainly kaolinite and Ca-montmorillonite. The dissolution of dolomite and carbon dioxide, and the precipitation of calcite change the concentration of bicarbonate ions in the pregnant solution. While the dissolution of feldspar and clay minerals, and the precipitation of mica change the concentration of silicon in the pregnant solution. It shows that mineral dissolution will cause TDS rise and mineral precipitation (such as muscovite, calcite, kaolinite and Ca-montmorillonite) in the desalination process. Identification of water-rock reaction in the in-situ leaching desalination process by inversion simulation, the water-rock reaction and reaction degree are preliminarily understood, which provides a basis for the subsequent identification of water-rock reaction in in-situ leaching of uranium. Furthermore, mineral precipitation also provides a new idea for determining which mineral causes the change of ore bed porosity during in-situ leaching process.