How to promote the collaborative innovation of Industry-University-Institute knowledge alliance is an academic focus and a realistic problem. This article explores the collaborative innovation mechanism of Industry-University-Institute knowledge alliance from the enterprise perspective. This article draws the following conclusions: (1) The individual-individual mode and the organization-individual mode in knowledge sharing modes have extremely significant positive effects on enterprises' innovative performance, and the organization-organization mode in knowledge sharing modes has a very significantly positive effect on enterprises' innovative performance. The enterprises in Industry-University-Institute knowledge alliance can promote their innovation performance through knowledge sharing. although scholars in knowledge management field have reached a consensus for it, there is few literature which classify knowledge sharing modes and validate the effect of different modes of knowledge sharing on enterprise's innovation performance based on empirical study. This article examines the degree of positive effect by analyzing 326 valid questionnaires, the result of which bridges the research gaps. (2) Theinter-organizational learning has an extremely significant positive effect on enterprises' innovative performance. The empirical result of this study provides a theoretical support for an increasingly collaborative innovation practice among Industry-University-Institute knowledge alliance. However, it is important to note that the individual-individual mode and the organization-individual mode in knowledge sharing modes respectively have significant and extremely significant positive effects on inter-organizational learning, but the organization-organization mode in knowledge sharing modes has a negative effect on knowledge creation in inter-organizational learning. The negative effect is not significant, but its reason should be explored further. Based on the perspective of resource and transaction cost, the Industry-University-Institute knowledge alliance just provides the opportunities of acquiring external knowledge for every organization, but whether it can take advantage of these opportunities for creating knowledge depends on the synergy of cultural identity, communication mechanism, interest mechanism, absorption capacity and ecological environment in alliance. The individual-individual mode and the organization-individual mode have higher flexibility, they are seldom affected by the above factors, hence more likely to help acquire and create knowledge. (3) The intermediary effect of inter-organizational learning in the relationship between the individual-individual mode in knowledge sharing modes and enterprises' innovative performance is partly established, the intermediary effect of inter-organizational learning in the relationship between the organization-individual mode in knowledge sharing modes and enterprises' innovative performance and the intermediary effect of the knowledge acquisition in inter-organizational learning in the relationship between the organization-organization mode in knowledge sharing modes and enterprises' innovative performance are fully established. The study conclusion proves that knowledge transfer parties in the Industry-University-Institute knowledge alliance can promote the innovation performance through inter-organizational learning; however, it has discovered that lacks extent and depth to some extend. The collaborative innovation of Industry-University-Institute knowledge alliance fails to improve enterprises' innovative performance based on the organization-organization mode and through knowledge creation.