Among comprehension instructions that encourage collaborative learning, Collaborative Strategic Reading (CSR) and Questioning the Author (QtA) were known for their effectiveness. Both help students on improved comprehension of text and building a positive relationship among themselves. Similarly, Ability Grouping and Self-efficacy were factors that gave a significant impact on students' reading comprehension. Ability grouping affected students' reading by helping them achieve psychological intimacy and integrated involvement. On the other hand, self-efficacy determined students' achievement based on their self-confidence. Many researchers have conducted studies on CSR, QtA, Ability grouping and self-efficacy. However, there was no study that examined the effects of CSR and QtA on students' reading comprehension viewed from students' ability grouping and self-efficacy. For that reason, this study is aimed to explain the impact of two comprehension strategy instructions (CSR and QtA), two kinds of Ability Grouping (Homogeneous and Heterogeneous), and two level of students' self-efficacy beliefs (High and Low) on students' Reading Comprehension by conducting an experimental study which adopted 2x2x2 factorial design. Moreover, the study also described the interaction between those variables. It took one hundred and twenty-one of first semester students in Universitas Dehasen Bengkulu as the participant. The study administered a Reading comprehension of TOEFL test to decide students' ability grouping. A Reading Self-Efficacy Questionnaire developed by Piercey was used to measure students' self-efficacy on reading. Moreover, a reading test was developed for measuring students' Reading comprehension which was analyzed by using t-test, and three-way Anova. The result showed that 1. Comprehension instructions, ability grouping, and self-efficacy gave a positive effect on students' Reading comprehension, 2. There was an interaction between Comprehension Strategy instruction and Ability Grouping, 3. There was an interaction between Comprehension Strategy instruction and self-efficacy, 4. There was not any interaction between ability grouping and self-efficacy, 5. There was an interaction between Comprehension Strategy instructions, ability grouping, and self-efficacy.