Abstract: Using the data of 371 Chinese innovation-oriented firms, this paper empirically tested the relationship between independent R&D and innovation performance, and on this base, we have further probed the moderating effects of region-specific institutions. By these results, we have discovered that, （1）independent R&D has significant positive influence on innovation performance.（2）domestic firms in different regions of China do not equally benefit from independent R&D. Firms that operate in regions with higher levels of international openness, intellectual property right protection and market development are better able to use independent R&D to improve their innovation performance. (3) The results also reveal that the moderating effects of region-specific institutions depend on the ownership types of firms, and whether they have been listed or built oversea R&D centers. Our studies have important enlightenment for understanding the role of region-specific institutions in firms’ innovation process, and promoting the strategy of innovation-driven development.