•The impact of environmental regulation on industrial structure upgrading is explored.•The perspective of strategic interaction between local governments is considered.•The spatial panel Durbin model is used in this paper. Promoting the industrial structure upgrading is the key path to guide the high-quality development of a country's economy. Based on the perspective of strategic interaction between local governments, using the panel data of 30 provinces in China from 2004 to 2017, this paper makes an empirical analysis on the impact of environmental regulation on the upgrading of industrial structure with the help of spatial panel Durbin model. The results show that: (1) There is a significant positive spatial correlation in the upgrading of industrial structure during the sample period. (2) There are regional differences in the impact of environmental regulation on the upgrading of industrial structure. Under the national sample and the eastern sample, there is a positive correlation between environmental regulation and the upgrading of industrial structure; under the sample of the central and western regions, there is a negative correlation between environmental regulation and the upgrading of industrial structure. (3) The strategic interaction of environmental regulation among local governments has a differential impact on the upgrading of industrial structure. Under the national sample, the “imitation” strategy is generally adopted, which is specifically manifested as “Race to the Bottom”.