Palestine is one of the developing countries that have recently realized the benefits of e-commerce (EC), but several barriers are impeding its adoption there. This study highlights the major barriers to EC adoption in Palestine using a TOE framework, the model of innovation resistance, and other related theories such as diffusion of innovation (DOI). An online survey collected data from 161 business owners in Palestine, and the model has tested through structural equation modeling (SEM) to analyze the survey respondents. The study has found that the occupation restrictions and the political factors are the major barriers that prevent the adoption of ecommerce in Palestine, while it has found that some barriers have weakly affected the adoption or had no influence, such as perceived financial losses. It is expected that this research will benefit many parties in Palestine, by being the first of its kind to tackle the occupation’s impact on EC in Palestine, and that by avoiding such barriers investment in EC will increase in Palestine in the future.