The article divides entrepreneurship variable into two variables of entrepreneurship spirit and innovation spirit. Based on the panel data of 30 provinces during 2000-2015 in China and the DEA-Malmquist index approach, we calculates the indices of China’s total factor productivity. At the same time, applying a fixed effects model, this study tests the influence of entrepreneurship spirit and innovation spirit on China’s total factor productivity. The estimation results show that both entrepreneurship spirit and innovation spirit have positive effects on China’s total factor productivity growth, a variety of robustness tests confirm the above result once again. Based on the result of empirical analysis, we put forward some countermeasures and suggestion in increasing entrepreneurship spirit and innovation spirit to promote regional total factor productivity.