Under the dual circulation development pattern, further expanding the opening-up will be the key to building a national unified market in China. Based on the analysis of the theoretical mechanism of opening up to the outside world, this paper constructs a spatial econometric model to test the spatial spillover effect of opening up to the outside world on China’s market segmentation by selecting Chinese provincial panel data from 2005 to 2020 and testing the theoretical mechanism through a mediating effect model. The study shows that: opening up to the outside world can significantly reduce the degree of market segmentation in the region with positive spatial spillover effects; the test of theoretical mechanism further finds that opening up to the outside world breaks the market segmentation through three paths of reforming the shareholding system of state-owned enterprises, building infrastructure and improving the level of regional economic development, and has a positive effect on the construction of a unified national market.