As the core element of classroom teaching, questions play an essential role in constructing students' knowledge systems and cultivating their ability to discover, explore, analyze, and solve problems. Therefore, the design and application of appropriate questions is the key to the success of classroom teaching. Teaching based on protocol-guided cases advocates question-centric teaching. It is suggested that teaching activities should be carried out around the discovery and solution of questions, promoting the teaching concept to change from lecture to inquiry, stimulating students' interest and potential, and improving students' comprehensive quality. This article mainly discusses the design and application of questions in middle school protocol-guided learning and discusses the basis and requirements of question design in protocol-guided case. With typical cases as the forerunner, strategic guidance is put forward to apply questions to integrate teaching plans.