Abstract: Hydraulic conductivity in sandstone-type uranium-bearing formations is of high heterogeneity. However, restricted by the means of test and analysis, it is difficult to accurately describe the heterogeneous coefficient of permeability, which results in the deviation in the prediction of in-situ leaching uranium mining process and limits the fine control of in-situ leaching uranium mining process. To solve this problem, a random characterization method of heterogeneous parameter distribution of an ore bed is proposed in this paper. On this basis, water salt coupling numerical random simulation is carried out to reveal the internal migration process and influence range of leaching agent reservoir caused by pumping and injection of multiple wells under the conditions of different spatial distribution of coefficient of permeability. The application results in a uranium deposit in Inner Mongolia show that the coefficient of permeability increases along the direction of regional groundwater flow, which is conducive to the evacuation of the injected leaching agent. On the contrary, the leaching agent is prone to the aggregation effect. After identifying and verifying the boundary conditions of the model with groundwater level monitoring data, the diffusion rate of the solution is 210 m²/d under the assumption of homogeneity, and the diffusion area of the 20-year mining cycle is 1.53 km². Considering the heterogeneity of the ore bed and the uncertainty of parameters, the expansion rate of the leaching agent area is predicted to be 191−228 m²/d, and the diffusion area of the leaching agent is 1.47−1.74 km². Compared with the assumption of homogenization, the uncertainty of the diffusion rate and diffusion area of the leaching agent is 17.62% and 17.65%. Considering the heterogeneity and uncertainty of coefficient of permeability, the prediction results of leaching agent migration and transformation behavior are more representative, which provides a more reliable reference for the design of in-situ leaching uranium mining scheme and the development of sandstone type uranium resources.