This study aims to provide insights into the role of learners' knowledge structures about a socio-scientific issue (SSI) in their informal reasoning on the issue. A total of 42 non-science major university students' knowledge structures and informal reasoning were assessed with multidimensional analyses. With both qualitative and quantitative analyses, this study revealed that those students with more extended and better-organized knowledge structures, as well as those who more frequently used higher-order information processing modes, were more oriented towards achieving a higher-level informal reasoning quality. The regression analyses further showed that the "richness" of the students' knowledge structures explained 25% of the variation in their rebuttal construction, an important indicator of reasoning quality, indicating the significance of the role of students' sophisticated knowledge structure in SSI reasoning. Besides, this study also provides some initial evidence for the significant role of the "core" concept within one's knowledge structure in one's SSI reasoning. The findings in this study suggest that, in SSI-based instruction, science instructors should try to identify students' core concepts within their prior knowledge regarding the SSI, and then they should try to guide students to construct and structure relevant concepts or ideas regarding the SSI based on their core concepts. Thus, students could obtain extended and well-organized knowledge structures, which would then help them achieve better learning transfer in dealing with SSIs.