Abstract: The science and technology innovation base (STIB) is the first echelon of national strategic science and technology force. Universities are the main supporting units of STIB. However, few studies have answered the question of whether establishing STIB can promote the development of science and technology innovation in universities by empirical analysis. Based on the mixed cross-sectional data of 394 universities in China from 2008 to 2017 and the typical STIB data, this paper examines the influence of the establishment of STIB on science and technology innovation in universities by using the differences-in-differences (DID) method. In addition, the heterogeneity test is carried out according to the different regions and administrative departments. The empirical results show that establishing STIB significantly improves the science and technology innovation in universities. Moreover, the establishment of STIB in the western region has the strongest influence on the level of scientific and technological innovation in universities, followed by the central region, while the eastern region has no significant influence. In addition, the degree of positive influence of STIB on the science and technology innovation of universities in the different administrative departments is similar. Therefore, the administrative departments should take policy guidance to give full play to the guiding role of STIB for the science and technology innovation in universities. At the same time, the construction of STIB of universities in the western region should be given more attention. In addition, various measures should be taken to ensure the science and technology innovation activities in the STIBs, thereby driving the development of science and technology innovation in universities.