The relationship between inquiry-based learning and science self-efficacy was analysed using data from 57 countries and economics participating in the 2015 Programme for International Student Assessment (PISA). This analysis generated a mediating--moderating model, which involved the mediating role of science interest and the moderating role of teacher support. The results indicated that (1) inquiry-based learning had a significant positive correlation with science self-efficacy; (2) science interest partially mediated the relationship between inquiry-based learning and science self-efficacy, with an indirect effect accounting for 20.1% of the total effect; and (3) teacher support moderated the direct effect positively while moderating the indirect effect negatively. These details of the link between inquiry-based learning and science self-efficacy provided theoretical guidance and practical support to improve the application of inquiry-based learning in science education.