This study aims to establish a model-based approach for user interface design that simultaneously considers the system’s information hierarchy, users’ task procedure knowledge, and system interfaces. The approach is based on a framework that contains multiple interaction models to express both system elements and users’ knowledge. In evaluation processes, the framework, referred to the CDI (Combined Difficulty Index), evaluates system interface by the relation structure of users’ task knowledge, information acquisition, and users’ task procedure. In the design process, the information structure of a designed system is validated according to whether or not it matches users’ task knowledge, and the interface is evaluated by its contribution to the users’ task performance and navigation of the system information structure. Through the crosscheck process of models, the relation between information, interface, and task procedure is calculated. A user test was conducted for the validation of the CDI. The difficulties of the interface of a mobile healthcare system were predicted with the CDI, and the predictions were compared with the experimental results, where the users’ performance showed consistence with the prediction.