This paper establishes the energy balance equation of a story isolation structure at the moment that the maximal seismic responses occur. The maximal deformation ratio between the isolation layer and the sub-structure is solved by RSS(root sum square) method. The expressions of the total elastic vibration energy, the hysteretic damping dissipated energy by the lead dampers in isolation layer and the viscous damping dissipated energy of the sub-structure are presented. Through introducing the concept of design energy spectrum, the formulas to predict the seismic responses are derived based on the energy balance equation. Finally, the 12-story story isolation structures with three various isolation layer locations are used as a numerical example to validate the accuracy of the predicted responses. Results indicate that the response prediction curves can match well and envelope most of the time history responses for a class of earthquake records.