DMFC(Direct Methanol Fuel Cell) is one of promising candidates for power sources of small mobile IT devices like notebook, cell phone, and so on. Efficient operation of fuel cell system is very important for long-sustained power supply because of limited fuel tank size. It is necessary to investigate operation characteristics of fuel cell stack for optimal control of DMFC system. The generated voltage was modeled according to various operating condition; methanol concentration, stack temperature, and load current. It is inevitable for methanol solution at anode to cross over to cathode through MEA(membrane electrode assembly), which reduces the system efficiency and increases fuel consumption. In this study, optimal operation conditions are proposed by analyzing stack performance model, cross-over phenomenon, and system efficiency.