Students with disabilities encounter many difficulties in learning activities, especially in reading. To help them participate in reading activities more effectively, this study proposed an integrated reading support system based on the principle of multiple representations. An integrated e-reading support system provides physical, sensory, and cognitive support to learners. This system also served as the convenient interface for material developers and instructors. The results of usability evaluation also demonstrated the interface of learner to be friendly and efficient. Thirty fifth- and sixth-grade students with learning disabilities in Taiwan participated in the experiment to explore if this e-reading system could help them to understand natural-science articles. All students read the articles on the e-reading system, with and without cognitive support. The results indicated better comprehension performance when the participants read with cognitive support. (Contains 2 tables and 2 figures.)