In China, after experiencing high resource dependence (RD) and extensive development, some regions that once had abundant resource reserves have fallen into a state of long-term economic stagnation. Therefore, an in-depth analysis of the relationship, the influencing mechanisms, and the key influencing factors between natural resources and regional economic development will help to clarify the change in and the development of China’s resource-based regions. This study takes 19 resource-based provinces in China as the research object, and it builds an analysis model that includes the regional economic growth, the RD, the institutional quality (IQ), the technological innovation (TI), and other variables, on the basis of panel data from 2000 to 2019. China’s actual research conclusions. First, there is a substantial negative correlation between RD and economic development; that is, at the current stage of economic development in the sample provinces, the resource-curse (RC) phenomenon exists, and RD has become an obstacle to economic growth. Moreover, through further research, we find that institutional relationships between quality and economic growth are not apparent, but there is a significant positive correlation between the interaction term of the IQ and RD and economic growth. Finally, TI plays an important intermediary function in the relation between RD and economic growth; high-quality TI can significantly reduce the adverse impact of RD on economic growth. The conclusions of this study help enrich the connotation of the “resource curse” theory in terms of emerging economies, and the policy implications have guiding significance for China’s ongoing “regional economic transformation and sustainable development.”