Abstract: Regional innovation system is an important method to enhance regional innovation capability. The construction of regional innovation system not only benefits from the drive of indigenous innovation subjects, but also is inseparable from participation of innovation resources from external region under open condition. Driven by large-scale overseas R&D investment of MNCs, MNCs overseas R&D institutions and regional innovation system of host country are influenced and interacted mutually, and gradually form the interactive relationship. Based on the background of R&D globalization, combing and summering the related literature reviews, the paper firstly probes into the evolution of development between MNCs overseas R&D institutions and regional innovation system of host country, and analyzes the interactive relationship between MNCs overseas R&D institutions and regional innovation system of host country in different stages from the perspective of evolution. And then discusses the formation mechanism of interaction between MNCs overseas R&D institutions and regional innovation system of host country according to the interactive intentions and elements. Finally, the Microsoft is taken to be the typical example so as to analyze the interactive relationship between MNCs overseas R&D institutions and innovation subjects in China.