A significant portion of the hanging ore surrounding a large open-pit mine, accounting for approximately 85.76 % of the resource beyond the open-pit boundary, is planned to be recovered using an upward drift mining and filling method. To isolate the mutual influence between open-pit and underground mining and ensure the safety of both the steep high slopes and underground operations, it is necessary to detern ea reasonabl thickness for the isolation pillars between the slope and underground stopes. Due to the influence of intersecting faults, the northwestern slope area has relatively poor stability and was selected as the study area. Laboratory tests were conducted, and initial pillar thicknesses tests were estimated based on empirical formulas and references from similar mines. Numerical simulation was then employed for optimization. Considering overall slope stability, a reasonable and safe thickness for the slope isolation pillar was proposed. The results show that, based on simulations using the Flac software, in combination with empirical calcula-tions and previous research, the optimal thickness of the isolation pillar in the northwestern slope area is >45 m. These findings provide a theoretical basis and practical reference for mine design and production.