Abstract: Groundwater plays a critical role in influencing the stability of open-pit slopes. Fluctuations in groundwater levels can occasionally result in significant property damage and casualties for these slopes. The present study aims to investigate the potential impact of future changes in groundwater levels on mining safety at Husab Open-pit Uranium Mine in Namibia, with a specific focus on the west side slope that contains weak interlayers. Firstly, the geological conditions of west side in the mining area are analyzed. Subsequently, a groundwater level contour network is constructed for the mining area, followed by an analysis of lithologic permeability. Finally, predictions are made regarding the future water inflow in the mining area during later stages of mine operation. The results indicate that the rock permeability of west side bedding slope with weak interlayers is the highest, ranging from 6.00-9.98 m²/d, and its water level contour is 440 m amsl. Furthermore, as mining progresses deeper, there is a linear increase in water inflow within the mining area, which can potentially have adverse effects on the stability of the side wall and foot of the slope. The safety calculation is performed using the finite element method（FEM） program RS2 and the limit equilibrium Slide software when the slope transitions from a dry state to a saturated state. The slope safety factor, as calculated by RS2, experienced a significant decrease of 62% from 1.33 to 0.50 due to the anticipated increase in water inflow. Slide’s calculation also reveals a reduction in the slope’s safety factor from the range of 1.2-1.3 to 0.7-0.9, representing a decrease of approximately 31%-42%. It is worth noting that joint cracks and weak layers exhibit heightened sensitivity towards water. The deepening of the mining area will render groundwater a crucial factor impacting mine safety, as water infiltration weakens the strength of bedding slopes containing vulnerable interlayers, leading to severe disasters. The research findings present in this paper will offer valuable guidance for subsequent safe mine operations.