Disclosed is a system and method for controlling pressure oscillation in an anode of a fuel cell stack. In particular, an electronic control unit is configured to determine operation information including a reference power mapped based on the operating pressure of a fuel cell system and a reference differential pressure between at least two predetermined points in a vicinity of the anode, compare the power of the fuel cell system with the reference power and, when the power is less than the reference power, control the pressure in the anode to be an oscillating target pressure, and compare the measured differential pressure between the at least two points with the reference differential pressure and, when the measured differential pressure is less than the reference differential pressure, reduce a purge valve operation cycle.