Abstract: The Yangtze River Economic Belt Development Strategy is a major regional development strategy after China has entered a new stage of development. The implementation has an important impact on the development of the Yangtze River Economic Belt. Based on the panel data of prefecture-level cities from 2005-2019, this paper used the difference-in-differences method to study the effects and mechanism of the implementation of the Yangtze River Economic Belt Development Strategy on the industrial structure upgrade of this region. It was found that the implementation of the Yangtze River Economic Belt Development Strategy significantly promoted the advancement and rationalization of industrial structure in the Yangtze River Economic Belt, which was still valid after multiple robustness tests. According to the sustainable development theory, this effect was mainly achieved through three aspects: environmental regulation, innovation and infrastructure construction. Heterogeneity tests showed that the Yangtze River Economic Belt Development Strategy significantly promoted the rationalization of industrial structure in riverine cities and polluting cities, but not the advancement of industrial structure; For non-riverine cities, the Yangtze River Economic Belt Development Strategy significantly promoted the advancement of industrial structure, but not the rationalization of industrial structure; For non-polluting cities, the Yangtze River Economic Belt Development Strategy significantly promoted both the advancement and the rationalization of local industrial structure. These findings may provide theoretical support and policy enlightenment for the further implementation of the Yangtze River Economic Belt Development Strategy.