The nonlinear dynamic response analysis of substation with structure-equipments interaction is studied in this paper. The results comparing with that of no interaction are shown that it’s necessary to considering structure-equipments interaction in substations. In frequent earthquakes, the structure-equipments interaction in substation is inconspicuous and the traditional equivalent load method is feasible. However, in strong earthquakes, the electric equipments really participate in the dynamic response and operate the reaction on main structure and the action goes against the main structure seismic design and couldn’t be ignored. In this condition, the traditional equivalent load method will be insecure any more. Because of the visible torsional response effect, the seismic ability of the corner columns in structure should be increased. The research results can be referenced by similar lifeline system.