Since the efficiency of fuel cells is the ratio of the electrical power output and the fuel input, it is a function of power density, system pressure, and stoichiometric ratios of hydrogen and oxygen. Typically, the fuel cell efficiency decreases as its power output increases. In order for the fuel cell system to obtain highly efficient operation with the same power generation, more cells and other auxiliaries such as a high-capacity compressor system, etc. are required. In other words, fuel cell efficiency is closely related to fuel cell economics. Therefore, an optimum efficiency should exist and should result in the definition of a cost-effective fuel cell system. Using a multi-objective optimization technique, the sequential quadratic programming (SQP) method, the efficiency and cost of a fuel cell system have been optimized under various operating conditions. This paper has obtained some analytical results that provide a useful suggestion for the design of a cost-effective fuel cell system with high operation efficiency.