This research focuses on modeling the relationships between operating parameters and performance measures for a single stack direct methanol fuel cell (DMFC). Four operating parameters, including temperature, methanol concentration, and methanol and air flow rates, are considered in this work. Performance of the DMFC is described by the relationship between current density and voltage. The open circuit voltage and voltage drop in the closed circuit due to resistance, activation, and concentration polarization are influenced by the operating parameters. To consider both modeling accuracy and simplicity, a semi-empirical model is developed in this work by integrating theoretical and approximation models. Experiments were designed and conducted to collect the required data and to obtain the coefficients in the semi-empirical model. The error analysis indicates that our semi-empirical model is effective for predicating the DMFC's performance. The influence of the four operating parameters on the DMFC's performance is also analyzed based on this semi-empirical model. Possible applications of the semi-empirical model in the optimal control of fuel cell systems are also discussed. (C) 2011 Elsevier B.V. All rights reserved.