Abstract:Science-based innovation is defined as innovation driven by frontier scientific knowledge, and SRDI "Little Giant" enterprises occupy a key position in the innovation chain. Adopting a Co-Innovation perspective and drawing on the Knowledge-Based View, this paper conceptualized Industry-University-Research alliances as the core organizational vehicle of Co-Innovation, and examined their impact on Science-based Innovation in SRDI "Little Giant" enterprises as well as the underlying mechanisms.It is found that IUR alliance participation significantly raises the level of science-based innovation, mainly through an expanded breadth of knowledge search, and government R&D subsidy intensity positively moderates the alliance–innovation link; the alliance effect is stronger for private enterprises, strategic emerging-industry firms, and firms located in birthplaces of traditional business-clan culture. The influence mechanism of IUR alliance on science-based innovation is clarified under the co-innovation framework, micro-level research on science-based innovation is extended, and practical guidance is provided for SRDI "Little Giant" enterprises to strengthen their innovation leadership and to improve supply-chain coordination and resilience.