Abstract Based on the balanced panel data of 31 provinces (autonomous regions and municipalities) in China from 2005 to 2019, this paper discusses the impact of intra-regional cooperation, inter-regional cooperation and the balance of intra-regional and inter-regional on regional innovation performance based on knowledge production function. On this basis, the moderating role of regional technological diversification as a situational factor is also analyzed. The results are listed as follows. The innovation performance of each region has improved significantly, but the gap between the central and western regions and the eastern region has not been significantly improved. Under the geo-spatial effect, intra-regional cooperation significantly promotes the improvement of regional innovation performance. Although there is a non-linear relationship between inter-regional cooperation and regional innovation performance, with the increase of cross-regional cooperation, regional innovation performance shows an inverted U-shaped trend of rising first and then decreasing. Different from the positive correlation in previous studies, this study points out from the perspective of resource scarcity that the balance of intra-regional and inter-regional cooperation is not conducive to the improvement of regional innovation performance. Regional technological diversification not only directly improves regional innovation performance, but also positively adjusts the relationship between intra-regional, inter-regional and their balance and regional innovation performance.