Abstract: Saltwater intrusion was the salinity diffusion process by the tide and runoff into the sea. In this paper, the theory of energy accumulation and impedance was used as the basis by which to analyze and infer the diffusion response function of runoff into the sea, tidal range and region of intrusion, and the data of runoff into the sea, tidal range and region of saltwater intrusion over the last 50 years was analyzed and calculated to confirm the theory. The results indicated that the function between the tidal range and region of intrusion exhibited obvious S-shaped regularity, and there was the same S-shaped conclusion between the runoff into the sea and maximum area over the standard salinity, which formed a three-dimensional diffusion response function of saltwater intrusion. Using the data over the last 50 years in the Yangtze River Estuary, the three-dimensional diffusion characteristic was confirmed, the S-shaped function based on the hyperbolic tangent of saltwater intrusion was constructed, and the parameter setting and quantization method was given. Through the theory of this function, the runoff into the sea which controls the saltwater intrusion was ascertained to be 10 000 m³/s, and the loss caused by the saltwater intrusion was further calculated over 2001-2012.