A pressure control system of a fuel cell stack includes: an air supply control unit for controlling a revolutions per minute (RPM) of an air compressor for supplying air to a cathode side of the fuel cell stack based on a required output of the fuel cell stack; a hydrogen supply control unit for controlling a pressure at an anode side of the fuel cell stack with a target pressure based on the required output of the fuel cell stack; and a differential pressure control unit for controlling the air supply control unit or the hydrogen supply control unit to calculate a differential pressure between the anode side and the cathode side of the fuel cell stack, and to modify the target pressure or the RPM of the air compressor based on the calculated differential pressure.