The output power efficiency of the fuel cell system depends on the anode pressure, cathode pressure, temperature, demanded current, air and hydrogen humidity. Thus, it is necessary to determine the optimal operation condition for maximum power efficiency. In this paper, we developed a dynamic model of fuel cell system which contains mass flow model, membrane hydration and electro-chemistry model. Experiments have been performed to evaluate the dynamical Polymer Electrolyte Membrane Fuel Cell (PEMFC) stack model. In order to determine the maximum output power and minimum use of hydrogen in a certain condition, response surface methodology optimization based on the proposed PEMFC stack model is presented. The results provide an effective method to optimize the operation condition under varied situations.