Abstract: This paper integrates the knowledge-based view and innovation management theory, and studies the impact of knowledge couplings on firms’ radical innovation, and the moderating effect of firms’ technological diversity on the relationship between knowledge couplings and firms’ radical innovation, by the panel data of 142 listed Chinese firms during 2010 to 2014 and using random-effects negative binomial regression model. Our findings reveal that the couplings among existing knowledge domains has a negative effect on firms’ radical innovation, and the couplings new and existing knowledge domains has a positive effect on firms’ radical innovation. The results also show that firms’ technological diversity positively moderates the relationship between the couplings among existing knowledge domains and firms’ radical innovation, but negatively moderates the effect of the couplings new and existing knowledge domains on firms’ radical innovation. We develop arguments to explain how changes in knowledge base affect the generation of radical innovation. This paper enriches the research production of knowledge and innovation management, and provides a theoretical basis for firms’ radical innovation to choose the appropriate knowledge couplings.