Two-dimensional coupling model of water quality and water quantity was established. Then a random function module and Regionalized Sensitivity Analysis (RSA) function were added into the model. Taking total nitrogen of Taihu lake for example, the paper used RSA method to analyze the parameter sensitivity of established model. The results show that organic sedimentation rate VS3 is the most sensitive and has greater influence on the simulation result of total nitrogen; the parameter sensitivity of each subarea in Taihu Lake is different,the sensitivity order of acceptably parameters for Pingtaishan monitoring point is VS3 > Kpzd > K12 > K71 > K2 > VS4 > K2D > GP1,and the parameter sensitivity order of East Lake 34 is: VS3 > VS4 > Kpzd > GP1 > K2D > K12 > K71 > K2. The research indicated that the difference of model parameter sensitivity is mainly owing to water quality conditions and variation of water environment in different subareas, which means that the sensitivity of parameters is also different with the environment changes of simulated subarea. The article determined a set of sensitivity analysis method of model parameter and can provide a reliable basis of parameter selection for application of water quality model in governance and plan of water environmental pollution.