Qianhai collaborative zone and Hengqin collaborative zone，which play as “bridgeheads” links with Hong Kong and Macao，are the most forward position to promote high-level opening up and the international scientific and technological innovation center building of the Guangdong-Hong Kong-Macao Greater Bay Area. In September 2021，the programs for the reform and construction of Hengqin collaborative zone and Qianhai collaborative zone were issued to expanding Qianhai district and upgrading Hengqin district. Institutional openness of innovation therefore become the key point of the “two collaborative zones” to achieve high-level reform and opening-up. Under this background and by the perspective of institutional openness，the paper discussed the economic，platform and environmental foundations for the innovative development of the “two collaborative zones”，and analyzed related difficulties and directions of institutional openness of innovative development from dimensions of direction，hierarchy，structure and effectiveness of institutional openness. Meanwhile，three principles of institutional openness of innovation for the “two collaborative zones” were proposed，such as persisting in reform and innovation of the system and mechanism，upholding the combination of points，lines and plane in the Guangdong-Hong Kong-Macao Bay Area，and adhering to the innovation main body status. Finally，to promote factor flow openness to institutional openness，some countermeasures for the “two collaborative zones” were putting forward such as focusing on institutional system construction，institutional docking，institutional guidance and institutional efficacy，etc.