Establishing a numerical model is an important approach of analyzing the evolution law of hydrodynamics and water quality of river. In the purpose of providing optimized topography data for numerical model, the nodes of the MIKE21 model boundary are equally spaced and coded to interpolate the measured topography of river section along the river bend direction. To verify the superiority of this method, a river segment of Jingmen City is selected as research object to illustrate the interpolation of topography data by Python programming. The terrains before and after the refinement processing are compared with the actual terrain. Results suggest that after the interpolation of measured cross-section, the river topography is refined, the operational error rate of model is reduced, and the modeling result is closer to the real situation.