Seismic isolation is a strategy to reduce damage of structures exposed to devastating earthquake excitations. Isolation systems, applied at the base of buildings, lower the fundamental frequency of the structure below the range of dominant frequencies of the ground motion as well as allow to dissipate more energy during structural vibrations. The effectiveness of the base-isolated buildings in damage reduction has been confirmed numerically for the models of structures with fixed supports. The aim of the present paper is to show the results of the non-linear analysis of the response of a base-isolated building supported on soft soil incorporating soil-structure interaction. The detailed study has been conducted for the building equipped with high damping rubber bearings used as isolation devices. The results of numerical simulations demonstrate that soil flexibility has a significant influence on the behaviour of isolated base of the structure. Considering the flexibility of soil significantly affects the rigid superstructure response lowering its potential to reduce structural damage.