The progressive collapse of a multi-story building and its protective effect with aluminum foam under an explosion in its basement are numerically investigated in this paper. The three-dimensional coupling model composed of a multi-story frame structure with a basement and the surround soil is modeled using ANSYS/LS-DYNA. The progressive collapse of the entire structure under explosive impact and the protective effect of the aluminum foam are simulated using the proposed three-stage simulation method (TSSM). The result shows that, the aluminum foam as a protective layer can reduce the impact effects very well, and then can prevent progressive collapse effectively. The same model is also simulated by direct simulation method (DSM) and alternative load path method (ALPM). By comparison with the two methods, the TSSM is illustrated practical, accurate and economic for the analysis of progressive collapse.