To quantitatively evaluate parameters influence and uncertainty of model, WASP model was reorganized by Simulink in this paper. Sensitivity of the parameters related to model output of DO, CBOD, NH3-N and NO3--N was studied based on Sobol method. In particular, sensitivity changes with temporal and spatial variations of input were discussed. Global sensitivity analysis of Sobol method can identify the most sensitive parameters of the process simulation; The significant difference between the total sensitivity and first-order sensitivity index showed that some parameters(e.g. GP1, PNH3, anc, etc.) of the WASP model were strongly coupling, andOne variable at a timemethod was inappropriate to evaluate the sensitivity of these parameters; Sensitivity index of WASP parameter changed with the temporal and spatial variation of boundary conditions, even for the same river; WASP model showed an obvious equifinality for different parameters, so the traditional methods such as the global optimization calibration, failed to simulate the mechanism process. Experiments were required as a verification for calibration of key parameters.