The sources in building fire are mainly solid combustibles. Based on the pyrolysis kinetics model of solid combustibles, a large eddy simulation (LES) is applied to the study of the interactions between the pyrolysis of the polyurethane foam (PUF) slab and the space fire spread and smoke flow in a multi-room building. The calculated mass variation rate of the PUF slab with time and the evolutions of the smoke temperature and CO2 and O2 concentrations in each room agree generally with the measured test data. The peak in the evolution of the CO2 concentration is high in the burn room and low in the neighboring rooms, while the valley in the evolution of O2 concentration is low in the burn room and high in the neighboring rooms. The peaks and valleys found in the evolutions of the smoke temperature and concentrations are relevant to the peak in the mass variation rate of the PUF slab with time.