Hybrid knife as a multi-function endoscopic instrument provides an effective model for endoscopic diagnosis and treatment of diseases. Hybrid knife does not need exchange of instrument during endoscopic operation. It can effectively reduce the potential risk of perforation and hemorrhage so that improving quality of life for patients. The technology has been widely used in clinic, especially in the treatment of digestive internal medicine, and in the course of respiratory intervention. Researchers have started to use the hybrid knife technique and have obtained good surgical results. In this review, we introduced the advantages of hybrid knife and summarized the clinic application, including the tumor excision and the tissue collection for pathology. Furthermore, the application of hybrid knife has significant implication to gastrointestinal and urinary diseases, and airway tumors, and we also explored the possibility of application of hybrid knife system in more diseases. Hybrid knife system has important clinical significance and is worth further study and exploration.