Abstract: The research object of this paper is a super high-rise building in Longgang district, Shenzhen, with a total building area of 127，262 m2. The main building is a frame-tube structure with 44 floors above ground and 3 floors underground. The foundation is in the form of boring cast-in-situ pile, of which 44% of the piles have been installed in the area of karst caves. The stability of the karst caves and their influence on the overall structure should be considered in the construction process. The interaction of the superstructure, foundation ground and the pile foundation should be analyzed. In this paper, a conceptual model for the interaction of the three complements was hence established. Using finite element method to simulate the stress, strain, displacement and mechanical behavior of the pile foundation was conducted. The simulated results were analyzed and compared with those obtained by traditional design method which separated the upper structure and the pile foundation into two independent parts with no interaction in the numerical simulation. The comparative results shows that the stress difference of pile foundation increases with the increase of pile foundation stiffness; and the difference may reach 18.2%. Meanwhile along with the increase of the pile foundation stiffness, the overall stress of pile group increases by 13.7% and the average foundation ground settlement decreases by 4.9%, leaving little effect on the difference of foundation ground settlement. The simulated results also show that the interaction of the superstructure, foundation ground and pile foundation has a minor stress on the secondary stress acts on the building pillars. However, the secondary stresses of individual angular pillar and the shear wall are much large. The arrangement of the latter has a great influence on the interaction; and the stress decreases rapidly with the increase of the floor. Through this study, it is realized that in a karst area raft foundation is a suitable one, as plays an important role in adjusting the interaction of the three components. Based on the interaction method for analyzing the interaction of karst foundation ground, boring cast-in-situ pile foundation and the upper structure, the calculation results of pile foundation stress are uniform, the difference of ground settlement is small, and the stiffness of the superstructure can effectively solve the problem of uneven settlement of the foundation ground, which suggests that the stability of the karst foundation is good.