Runoff, tides, riverbed morphology, and water intake influence saltwater intrusion in the Qiantang Estuary. Of these factors, runoff and tides are the decisive factors that determine whether the salinity at the intake exceeds the standard. Based on the main factors in saltwater intrusion, key issues in predicting the salinity-resisting discharge were analyzed, and a quantitative relationship regarding the response of the standard-exceeding time to the runoff and tidal range was established. A model for predicting the salinity-resisting discharge was built, and computational methods for parameters in the model were proposed. The prediction model was applied in the prediction of minimum salinity-resisting discharge in the Qiantang Estuary from 2012 to 2014. The validation results show that reservoir operation based on the predicted discharge can satisfy the salinity-resisting demand of Hangzhou City, and a discharge sufficient to resist saltwater intrusion must be guaranteed not only during spring tides but also during mid-and neap tides.