How to prevent and resolve COVID-19 pandemic and similar public health crisis is a significant research topic. Although research on science literacy has been involved in dealing with public health crisis, there is a lack of empirical tests between the mass public’s science literacy and co-production during COVID-19 pandemic. With the empirical evidence from 140 cities in China, the study finds that the public’s science literacy significantly promotes co-production in the battle against pandemic. Specifically, for every 1% increase in the mass public’s science literacy in the city, co-production increased by 14.2%. Meanwhile, regional education level and local government capacity can expand the positive role of the public’s science literacy on co-production to fight against COVID-19 pandemic. In addition, the performance of the public’s science literacy on co-production against pandemic shows heterogeneity at different stages of pandemic prevention, in different regions, and in cities of different scales. This study complemented the gaps in existing research on science literacy and co-production and empirically verified the potential positive role of the public’s science literacy in pandemic prevention and control. Furthermore, it provided new ideas for improving the effectiveness of public co-production in public health crisis governance.