In this paper, the smoke control effect of mechanical pressurization system in the vestibule of high-rise building are studied based on numerical simulation. The diversity of the actual air outlet setting of mechanical pressurization system is considered. The relative position of air outlet and fire door opening is investigated in our research, which is divided into three cases: directly opposite, diagonally opposite and perpendicular. The method of numerical simulation is used to study the influence of the relative position of the air outlet and door, as well as the installation heights of air outlet of the fire-induced smoke prevention system. The smoke control effect in the case of fire and the cold state without fire are compared and analyzed; the setting position of air outlet is optimized. The conclusion of this paper can provide some references for the specific setting of the air supply system in the vestibule, and it has a certain engineering practical significance.