An operation control method of a fuel cell system is provided that increases the output of a fuel cell stack by detecting and overcoming the cause of a performance limit when the stack reaches the performance limit during high-altitude operation of a fuel cell vehicle, thereby achieving higher stack performance and vehicle power performance. The method includes determining whether an operation state of the stack corresponds to a predetermined condition in which a stack output limit occurs by determining current operation state information of the stack. Additionally, operating pressure of an air pole is adjusted by changing an opening degree of an air pressure adjusting valve to a control command value based on the operation state of the stack when the operation state corresponds to the predetermined condition in which the stack output limit occurs.