Abstract: Innovation is the primary driving force of economic development. As the carrier of innovation activities, the spatial configuration distortion of industrial land and the impacts were the major issues related to the high-quality development of the regional economy. Based on the panel data of 41 cities in the Yangtze River Delta region from 2008 to 2019, this paper used the spatial econometric model and the intermediary effect model to investigate the impacts and mechanism of industrial land spatial mismatch on urban innovation. The results showed that: (1) From the perspective of industrial land misallocation types, most of the central cities in the Yangtze River Delta region were identified as deficient misallocation, while most of the peripheral cities were identified as excess misallocation. (2) During the study period, the innovation level in the Yangtze River Delta region was generally improved, and the improvement rate of peripheral cities was greater than that of central cities; In terms of space, the level of urban innovation decreased from east to west, and gradually formed a continuous innovation zone centered on Shanghai, Nanjing and Hangzhou. (3) The spatial mismatching of industrial land had a significant negative impact on urban innovation, and this negative impact was more obvious in areas with deficient mismatching, industries with high land dependence and for periods with strong land constraints; In excess mismatched areas, there existed a negative spillover effect of industrial land spatial mismatching. (4) For the excess mismatching area, the spatial mismatching of industrial land obstructed the improvement of the innovation level through the innovation capital extrusion mechanism and the innovation environment destruction mechanism; For the deficient mismatched areas, the spatial misallocation of industrial land mainly hindered the improvement of innovation level through the mechanism of innovation capital extrusion. This study implied that promoting the correction of industrial land spatial mismatch was an effective measure to break the barriers to urban innovation and help the high-quality development of the Yangtze River Delta region.