Uranium (U) contamination of groundwater at in-situ leaching uranium mines is a global environmental geological problem. Accurately predicting the transport range of U in the groundwater outside the in-situ leaching mining areas is crucial to radiation risk assessment. In this study, the migration range of groundwater U at different production times was quantitatively simulated and predicted by numerical simulation method from an acid in-situ leaching uranium mine. The numerical simulation results showed that the mining activities of in-situ leaching uranium significantly changed the groundwater flow field in the mining area, and depression cones were induced by the high ratio of pumping to injection inside the mining area. On the basis of flow modeling, the transport model of groundwater U without considering adsorption and the retardation transport model based on K_d value were established. According to the groundwater pH of production well and monitoring wells at different distances outside the mining area, different K_d value was assigned by regions. By comparing the simulation results of the two models, it could be found that when considering the adsorption-retardation effect of aqueous medium on groundwater U, the simulation results could be better fitted with the field monitoring data, indicating that the migration of U in groundwater was significantly retarded by the aqueous medium. The U reactive transport model showed that the migration distance and range were reduced by 53% and 41%, respectively. Besides, the model predicted that the migration distance of groundwater U in the mining area was 50 m after 5 years of mining, which was consistent with the monitoring results. It was proven that the numerical simulation method, as an effective tool, could be successfully used to predict the impact of in-situ mining on groundwater environment at the uranium mining site.