Abstract: Based on the analysis of the mechanism of scientific and technological innovation affecting total factor productivity of the manufacturing industry, this paper uses provincial panels to construct an index system to reflect the development level of regional scientific and technological innovation, and empirically tests the effect of scientific and technological innovation on total factors of the manufacturing industry. The research shows that scientific and technological innovation plays a significant role in promoting total factor productivity of the manufacturing industry. By dividing the region into eastern, central and western regions, this paper then finds that the impact of scientific and technological innovation on total factor productivity of the manufacturing industry has regional heterogeneity, showing a greater promoting role in the central and western regions than in the eastern region. Further, a spatial panel data model is constructed to show that this significantly promoting role lies not only in local areas, but also in the surrounding areas through the spatial spillover effect. Finally, according to the research conclusion, this paper puts forward countermeasures and suggestions to improve the level of scientific and technological innovation to enhance total factor productivity of the manufacturing industry.