The high-rise structure with multi-skirt building is used widely so as to satisfy the increasing requirement of use function. In high intensity area, the structure adopts the isolation technology to promote its seismic safety and protect equipment. But, the structure is complex, the horizontal and vertical stiffness are not uniform, so the relationship of parameters between main tower, skirt building and isolated layer will seriously influence its seismic behavior and isolation effect. The paper analyzes influence of different parameters on isolation effect, the results show that: when the stiffness ratio of isolated layer to main tower is N≤1/14, the ratio of number of floor of skirt building to main tower is 1/3~1/1.5, the stiffness ratio of skirt building to main tower is 0.42~1.1, and the mass ratio of skirt building to main tower is P≥1.1, the main tower can obtain better isolation effect; it is possible to overstate the isolation effect of the upper structure according to the rigid floor assumption, so the large podium must be supposed to be elastic. Above suggestion may provide some references to design the base isolated high-rise structure with multi-skirt building.