Abstract: This paper focuses on whether and how the depth of industry-university-research cooperation affects the total factor productivity in the national high-tech zone. Based on the data of 83 national high-tech zones from 2011 to 2018 and on the basis of overcoming endogeneity, this paper systematically expounds and tests the influence of the depth of industry-university-research cooperation on the total factor productivity of national high-tech zones. The study found that: The depth of industry-university-research cooperation has a significant positive impact on the total factor productivity improvement of the national high-tech zone; Promoting technological innovation and optimizing the efficiency of resource allocation are the important intermediary channels for the depth of industry-university-research cooperation to influence the total factor productivity of the national high-tech zone; The marginal impact of the depth of industry-university-research cooperation on the total factor productivity of the national high-tech zone is more larger in the central and western regions; The positive influence of the depth of industry-university-research cooperation on the total factor productivity of the national high-tech zone is sensitive to the degree of cooperation, which has a significant impact in the subsamples of deep cooperation , but not in the sub-sample of shallow cooperation. The research conclusion provides policy enlightenment for the government to optimize the promotion policy of industry-university-research cooperation and accelerate the high-quality development of the national high-tech zone.