Background: A retrospective study was carried out to determine the feasibility and safety of an extracorporeal-assisted intracorporeal sliding knot-tying technique in minimally invasive surgery in children. Materials and Methods: From June 2009 to December 2017, a total of 333 cases of pediatric minimally invasive surgery were performed using the extracorporeal-assisted intracorporeal sliding knot-tying technique. Polyester, polyglactin, and polydioxanone sutures were used for suturing and knotting. The average time used for knotting was recorded during the surgery. The patients were followed up for unraveled knots and recurrence of the diseases. Results: All 333 surgical procedures were performed successfully, including 152 cases of thoracoscopic diaphragmatic hernia repair, 151 cases of thoracoscopic diaphragmatic plication, 7 cases of thoracoscopic esophageal anastomosis, and 23 cases of laparoscopic esophageal hiatal hernia fundoplication. No serious complications or mortalities were observed. Twelve-month to 9-year follow-up showed that all pediatric patients recovered well and no recurrence or unraveled knots were found. Conclusions: This new knot-tying technique is safe and feasible for various minimally invasive endoscopic surgeries, especially for suturing tissues under tension, such as thoracoscopic diaphragmatic hernia repair, laparoscopic esophageal hiatal hernia repair, and fundoplication. All types of sutures can be used for this knot-tying technique. It is easy to learn and can be quickly mastered by doctors with endoscopic surgery experience.