Abstract: Based on the research of relevant literatures, this paper puts forward the theoretical model and related hypotheses about the influencing factors of knowledge collaboration of industry-university-research collaborative innovation. The statistical analysis of questionnaire data shows that, there are significant positive effects on the knowledge collaboration of industry-university-research collaborative innovation, such as collaborative willingness, knowledge heterogeneity and organizational knowledge ability. The complexity of environment has significant negative effect on the knowledge collaboration performance, and the knowledge collaboration mechanism plays a mediating role in the impact of factors on the performance of knowledge collaboration. The research conclusion provides useful reference for the collaborative innovation practices of industry - university - research.