Injecting mine water into deep formations via boreholes is an effective approach for groundwater protection. Horizontal water storage wells enable efficient geological storage, and cross-layer fracturing is key to large-scale implementation. Based on rock mechanical parameters from in-situ borehole cores, a cemented sandstone-mudstone-sandstone physical model was established. Physical simulations of cross-layer fracturing in horizontal wells were conducted to investigate fracture propagation and sensitivity factors. Results show that in-situ stress difference, injection rate, aquitard thickness, and vertical distance from initiation point to aquitard floor are four critical factors. Fracturing effectiveness increases with higher stress difference and injection rate, but decreases with greater aquitard thickness and larger vertical distance. Stress difference is the most sensitive factor, followed by injection rate, aquitard thickness, and vertical distance. For optimal field performance, horizontal wells should be placed in deeper sandstone layers to maximize vertical-to-minimum horizontal stress difference, combined with high injection rates, thin aquitard layers, and initiation points close to the aquitard floor. These findings support large-scale geological storage of mine water.