Recent international comparison studies such as the Programme for International Student Assessment (PISA) repeatedly argued that inquiry-based learning (IBL) indicated a negative effect on science literacy (SL). However, those studies included two limitations in revealing the relationship between IBL and SL as they did not consider (1) instructional quality and (2) different types of IBL. Accordingly, this study aimed to explore relationships between two types of IBL (open and guided) and SL, and how four types of instructional quality (classroom management, adaptative teaching, teacher–student relationship, and teacher support) moderated the relationships between IBL and SL. For this purpose, a PISA 2015 Finnish sample was used and analyzed by latent moderated structural equation modeling in order to explore the latent interaction between IBL and the quality of instruction. The results of this study presented that the teacher–student relationship was the most potent predictor of SL and moderated the effects of guided and open inquiry on SL. Classroom management also indicated moderation effects for both guided and open inquiry. Also, this study showed the overruling effect of open inquiry on guided inquiry in predicting SL.