A modified waveguide model for predicting the sensitivity of surface-relief guided mode resonance (GMR) biosensors is presented. The proposed model is a convenient and fast calculation method compared to the current optical simulation tools such as the rigorous couple wave analysis (RCWA). A systematic and theoretical discussion of the GMR geometric structure and sensitivity of the modified model for biosensing is also presented. For a given GMR material, the theoretical maximum sensitivity can be achieved by choosing the proper geometric structure from the model simulations. A comparison of the GMR biosensor sensitivity respectively calculated by the model and the RCWA method shows good agreement. Finally, a suspending GMR structure with a 4.5-fold increase in sensitivity compared to the traditional surface-relief GMR is proposed.