The output power efficiency of the fuel cell system mainly depends on the required current, stack temperature, air excess ratio, hydrogen excess ratio, and inlet air humidity. Therefore, the operating conditions should be optimized to get maximum output power efficiency. In this paper, a dynamic model for the fuel cell stack was developed, which is comprised of a mass flow model, a gas diffusion layer model, a membrane hydration, and a stack voltage model. Experiments have been performed to calibrate the dynamic Polymer Electrolyte Membrane Fuel Cell (PEMFC) stack model. To achieve the maximum output power and the minimum use of hydrogen in a certain power condition, optimization was carried out using Response Surface Methodology (RSM) based on the proposed PEMFC stack model. Using the developed method, optimal operating conditions can be effectively selected in order to obtain minimum hydrogen consumption.