In the new era, the national high-tech industrial development Zone is a powerful platform for implementing the innovation-driven development strategy and promoting China’s high-level development. An empirical study of panel data from 285 county-level cities in China during 2001-2022 was conducted using the binary difference method. The results show that high-tech enterprises have a noticeable promoting effect on improving the quantity of industrial structure. The transformation and upgrading of our industrial design by high-tech enterprises have significant cyclical heterogeneity. It has significantly enhanced the industrial system compared with the “growth type” and “mature type” national high-tech development zones. There is no apparent regional difference in the quality effect of high-tech enterprises on industrial structure upgrading. Still, there is an evident regional difference in the quantity and rationality of industrial structure height.