Owing to the popularity of tablet computers and smart phones, e-books have become an important medium for both formal and informal learning. However, conventional e-books are mainly designed to provide information in the form of multimedia, implying that students spend most of their time memorizing and comprehending what they read from e-books, while seldom engaging in higher order thinking. In this study, a problem-posing framework is proposed for developing an interactive e-book for guiding students to observe and pose questions. An experiment on an elementary school natural science course was conducted to demonstrate the effectiveness of the proposed approach. The participants were 46 fourth-grade students. From the experimental results, it was found that the problem-posing-guiding interactive e-book can significantly improve the students' learning achievements, critical thinking tendency, and deep motive. It was also found that the proposed approach did not increase the students' cognitive load owing to the provision of proper supports during the problem-posing process, which has generally been identified as a challenging task.