Abstract: The maximum riverbed erosion depth near the crossing tunnel is a key parameter for the tunnel design. And its reasonable determination can provide a critical design basis for project safety and reduction of investment. Based on the analysis of previous studies, a two-dimensional flow and sediment mathematical model was developed to predict the bed erosion depth at the tunnel location, based on a case study of the Shiyezhou river-crossing tunnel that would be constructed in the Yizheng waterway. The Yizheng waterway is a critical river section of the lower reaches of the Yangtze River, and the river-bed evolution in the past century is as follows: the head of Shiyezhou sandbar collapsed continually, the left branch developed slowly with the mainstream moving towards the right after the confluence, and the right inlet still played a dominant role. So it is very necessary to study the maximum bed erosion depth near the location of the river-crossing tunnel. After analyzing the incoming water and sediment conditions in the project reach, we verified the mathematical model based on the existing data of the river processes, the features of river flow movement and the law of sediment erosion and deposition. The calculated values agreed well with the actual measured values. After model calibration using hydrographic field data and data of the historical morphological changes in the Yizheng waterway, the discharge processes in 2007—2010, 1998, and of the three-hundred-year return period were determined as the adverse flow and sediment conditions with consideration of the incoming flow and sediment conditions. The simulated results are predicted with the survey data of river bed drilling, and eventually the predicted maximum erosion depths of the branch channel in the left and right are 10.85 m and 8.87 m respectively during different flow and sediment series. The results are sufficiently safe for the construction of the river-crossing tunnel project and will be a scientific basis for the engineering design.