With the development of the digital economy, industrial structure upgrading plays an important role in realizing high-quality development. Exploiting the quasi-natural experimental setting provided by the Big Data Comprehensive Pilot Zone (BDCPZ) policy in China in 2016, this study evaluates the impacts of the BDCPZ policies on regional industrial structure upgrading using a combination of propensity score matching and difference-in-differences (PSM-DID) with panel data of 30 regions for the period 2008–2021. The results are as follows: (1) BDCPZ policies significantly promote regional industrial structure upgrading. This finding holds after conducting the placebo test and replacing explained variables. (2) BDCPZ policies enhance upgrading through technological innovation and financial deepening. (3) Heterogeneity analysis shows that the promotional effect of BDCPZ policies on industrial structure upgrading is more obvious in economically developed regions, megacities, and east-central regions; overall, regions with high industrialization benefit more. These findings have important implications: First, they provide new empirical evidence from the perspective of policy evaluation on how the digital economy affects industrial structure upgrading. Second, this study sheds light on the mechanism underlying this relationship, helping us understand how the digital economy can further affect the development of the industrial structure. Third, the policy effect is heterogenous, providing a scientific basis for the government to formulate differentiated implementation policies for different regions. This can help local industrial transformation and upgrading, and economic development in these regions through the implementation of big data and digital technologies.