Will market segmentation hinder regional R&D innovation? This paper estimates the market segmentation index of 29 provinces, autonomous regions and municipalities from 2001 to 2016, and combines the regional innovation index and regional economic characteristics data to study how market segmentation affects regional innovation at the provincial and provincial levels. The results show that, overall, there is a significant spatial positive correlation between the provinces; the direct effect of market segmentation in the province, the indirect effect of market segmentation between provinces, and the total effect of both have significantly inhibited regional innovation. And the local market segmentation has a greater inhibitory effect on the improvement of its own innovation index than the market segmentation between provinces. Therefore, this paper believes that the promotion of interregional innovation can not be limited by local resource endowments and market structure. It should also guard against local protectionist behaviors and expand regional market competition, so as to better carry out regional division of labor and cooperation, and give full play to interregional Spillover effects of technological innovation.