Abstract: Since ancient times, Anhui has not only profound theoretical foundations of natural philosophy, but also deep cultural traditions of craftsmanship. Moreover, in the beginning of the cultural exchange between China and the West, a large number of knowledgeable people of science and technology have emerged. It proves that China has a profound historical origin of technological innovation and cultural confidence. China's technological innovation and entrepreneurship also need to demonstrate a high degree of cultural confidence. We should face up to and reshape China's outstanding traditional culture, and shape, reconstruct and boost the cultural self-confidence from the perspective of technological innovation and entrepreneurship in the exchange of mutual understanding between Chinese and Western civilizations, in the inheritance of ancient and modern science and technology culture, and in the improvement process of the actual scientific and technological institutional culture.