China Railway Express (CR Express) plays an important role in the China international trade logistics system. CR Express has always adopted a point-to-point direct transportation (DT) mode since its first opening in 2011, which contributed to the rapid development of China CR Express networks in the early stage. However, with the reducing of subsidies, the transit transportation (TT) mode appears which performs better with respect to the improvement of efficiency of CR Express transportation networks, and its high-quality and sustainable development. Therefore, a CR Express with mixed transportation modes of both DT and TT modes will be inevitable in the future. This paper proposes a layout optimization model considering both the two transportation modes. It takes the existing cities in CR Express as candidates and allows hub nodes to choose either DT or TT mode. A case study reveals that the DT mode is more suitable for cities with sufficient goods supply, while the TT mode is more suitable for those with insufficient supply of cargo. At the same time, Zhengzhou, Xi'an, Jinan, Urumqi and other cities in key geographical locations are important hub nodes of the network. The proposed layout optimization model of multiple transportation modes not only considers the current conditions of CR Express, but also takes into account the needs of high-quality development in future, which is believed to be able to provide helpful insight into the layout optimization of CR Express transportation networks and its sustainable development.@en