Abstract In the context of the continuous slowdown of China’s economic growth, the innovative production activities led by entrepreneur innovative spirit can transform basic knowledge and ideas into market-oriented goods through the intermediary role of entrepreneur human capital, thus promoting long-term sustainable economic growth. Based on the panel data of 30 provinces of China in 2011-2016 and the empirical analysis method of SYS-GMM, this paper constructs two econometric models of progressive relationships. And finds that the entrepreneur innovative spirit can significantly promote the long-term sustainable economic growth both in the whole country and in various economic regions, but the impact of entrepreneur innovative spirit on economic growth is different in different economic regions. The entrepreneur innovative spirit of the northeast region is showing great potential, the east region is still playing a leading role, the central region is in the growth stage, and the western region needs to continue to explore the entrepreneur innovative spirit. In general, the government needs to further improve the system and environment for cultivating entrepreneur innovative spirit, and provide reliable path support for the transformation of regional economic growth mode.