A three-dimensional nonlinear numerical model with inclined pressure was developed to compute the saltwater intrusion at the Yangtze River Estuary. The σ-transformation was introduced in the vertical plane to achieve the same lattices in the whole domain of interest. The mode-splitting technique splits the three-dimensional governing equations into the surface gravity waves (external mode) and the internal gravity waves (internal mode). And the external mode was solved by the improved double-sweep-implicit (DSI) finite difference method and the internal mode was solved by the Eulerian-Lagrangian method. The Eulerian-Lagrangian method could not only reduce the numerical diffusion but also increase the computational accuracy by the improvement of the finite difference scheme in the vertical direction. Application of the model to the Yangtze River Estuary was carried out for the calculation of the saltwater intrusion and the null point. Results of the temporal and spatial distribution of the flow velocity and the salinity coincide with the measured data quite well. The formation and location of the underwater sandbars in the North Channel of the Yangtze River Estuary are closely related to the local salinity, the null point, the predominant current and the residual flow.