Active learning is centered on students and encourages them to participate in various classroom activities, with the teacher as a facilitator. Students are expected to develop multiple 21st-century skills through an active learning process, including digital and scientific literacies. Numerous studies demonstrate that students lack digital and scientific literacy, necessitating the empowerment and improvement of both skills through active learning based on TPACK (Technological, Pedagogical, and Content Knowledge) (Tütüniş et al, 2022). The objective of this study was to investigate the effect of TPACK-based active learning on students' digital literacy and scientific literacy in Genetics. PBL (Problem-based Learning), RQA (Reading, Questioning, and Answering), and a mix of PBL and RQA are all examples of active learning approaches. TPACK-based active learning was used in the Genetics course because students perceive genetics as challenging. A pretest-posttest three-treatment design was adopted, with each learning model being applied to a group of students. This study uses parametric inferential statistical methods, using ANCOVA. Data on students' digital literacy and scientific literacy were obtained using pretest and post-tests. The results indicated no statistically significant difference between the three learning models. The students' digital literacy and scientific literacy both experienced an increase due to implementing the three learning models. The implications of this research are the three active learning models based on TPACK can promote students' digital and scientific literacies. Other educators can adopt the experience of teaching Genetics with PBL, RQA, and PBL-RQA to promote digital literacy and scientific literacy.