Quality by design(QbD) is based on reasonable science and quality risk management, starting from a predetermined quality goal, focusing on the understanding of products and processes and the systematic research and development methods of production process control.As a complex drug delivery system, the microsphere formulation is becoming a new favorite of major pharmaceutical companies due to some obvious clin. advantages, such as more convenient administration, super long-term sustained release, lower toxic and adverse reactions, higher bioavailability and better patient compliance.However, only a few businesses drive related product landing because of some tech. barriers, including but not limited to complicated preparation process and more difficulties in pilot scale-up.In this article, we introduce traditional preparation methods, explain the specific process using the QbD concept to develop microspheres, and provide guidance for the development of microsphere drug products in the future.