In this paper, the effect of the non-uniformity settlement of ground foundation on the upper frame structure is studied. It takes a four-story space frame structure with two spans as an example. The different pedestals are installed at the joint of column footing, which respectively form the fixed supported model and the elastic supported model. Basin shaped settlement is applied in each model. The result shows that the beams are principally suffered with the bending moment and the columns principally suffered with axial force, shear force and bending moment, and that the elastic support model has certain economy.