This study investigated the predictive effect of 11th grade Taiwanese students’ ( N = 878) self-assessed critical thinking, group participation self-efficacy, and active learning on their genuine learning interest (GLI) in socio-scientific issues (SSI). Results showed that active learning had a direct effect on GLI, while critical thinking and group participation self-efficacy had indirect effects on GLI as mediated by active learning. Critical thinking showed a significant direct effect on active learning, and a significant indirect effect on active learning that was mediated by group participation self-efficacy.