A model for predicting the steady-state response of a pH-based potentiometric biosensor immobilizing organophosphorus hydrolase (OPH) is developed. The model combines the processes of diffusion and enzymatic reaction in the membrane. Key factors influencing the system response, such as enzyme reaction order, Thiele modulus, and buffer concentration are discussed in detail. It is possible to obtain a good linear response by designing an enzyme electrode with a high enough Thiele modulus and by appropriately controlling added buffer concentrations. It is found that the model is in reasonable agreement with the experiment results.