Recently e-Book has been widely discussed and brought into public attention with the presence of Amazon Kindle and Apple iPad on the market. Forrester as a U.S. research institution estimated that the textbook will be the largest market for e-book reader within five years. Meanwhile, there are continuously releases of e-book contents free or commercially available on the shelves. If government agencies and industry companies can seize the initiative of the key factors of teachers’ willingness to utilize e-book reader and further transfer these into policy making and business marketing, Taiwan governments and companies can thus play a competitive advantage and mutual benefit from the world’s new trends. The purpose of the research is to investigate the influence factors of the willingness of teachers to use e-book reader in class. First, the main factors were selected through the literature review and filtered by relevant experts from academic institutes and industry fields. Next, Analytic Hierarchy Process (AHP) was applied to allocate the weights and ranking of the factors of the evaluation model. Last, the decisions were taken by laboratory analysis Decision Making Trial and Evaluation Laboratory (DEMATEL) to determine the correlation and causation among these dimensions. Based on the research findings, the functionality and convenience of the digital contents are the most influential factor and the price of e-book reader is the key to popularization. In conclusion, this research can be used as reference for educational institutions and some constructive recommendations are provided for future industry development and e-book content suppliers.