The super-efficiency DEA method was used to measure the efficiency of industry-university-research synergy innovation in the nine provinces of the Pan-Pearl River Delta from 2007 to 2016, and the Malmquist index method was used to investigate the efficiency dynamic changes. The Tobit model was used to verify the key effect factors to the synergy innovation efficiency. The results show that the innovation efficiency of the nine provinces tends to improve on the whole but there are also short-term fluctuations. Among them, the synergy innovation efficiency of Guizhou and Hainan province is relatively the lowest, while the synergy innovation efficiency of Guangdong Province is the highest in the Pan-Pearl River Delta region. The effect of technology progress on the efficiency of synergy innovation is the most obvious, while the contribution of changes in technology efficiency is relatively small.The result shows that there is still a lot of room for digging benefits from the management and system improvement. The “ability of universities to participate in cooperation and transfer knowledge”, “the ability of enterprises to absorb and apply knowledge”, “the degree of support from the government and financial institutions”, and “the cooperation relationship of industry-university-research” have a significant positive impact on the improvement of synergy innovation efficiency, and the role of government and financial institution support is the most obvious, while the influence of regional economic development is not significant.