A new method was proposed for the assessment of frame structure under seismic excitation in the lab with the consideration of pile-soil interaction. In this method, an inverse model was proposed to identify the dynamic response from the substructure, the model, which relates sensor's data to the working state of the piles in the test system, was used to reduce the errors caused by uncontrollable of substructure and uncertainty of soil.Test validation was conducted by an idealized frame structure separately in this model, equivalent linearization method and the rigid foundation assumption. Numerical simulation and the tests data show that, under seismic excitations, the soil would experience plastic stage at the beginning of the excitations, and the new proposed method had a great advantage in the simulation of the pile-soil interaction. For the top displacement in the test structure, maximum displacement was found in the inverse model, followed by the equivalent linearization method, minimum in the rigid foundation assumption; however, for the drift ratio and inter-story shear, the former order was inversed.