To enhance the recycling rate of express packaging and the efficiency of the reverse logistics system for express packaging, a bilayer programming model is adopted to address the location selection and route optimization of express packaging recycling centers. Firstly, the unsupervised and easy-to-operate K-Means clustering algorithm is used to determine the number and candidate locations of recycling centers. Then, the traditional genetic algorithm is employed to solve the upper-level model and determine the final locations of the recycling centers. Next, the improved genetic algorithm is utilized to solve the lower-level model and optimize the recycling routes to minimize costs. Finally, a simulation analysis is conducted using X enterprise in Qingbaijiang district, Chengdu as an example, which verifies the effectiveness of the bilayer programming model and the designed solution algorithms.