Hysterectomy is one of the most common surgical procedures in obstetrics and gynecology, which can be performed via abdominal, laparoscopic and vaginal approaches. In recent years, driven by the growing aesthetic demands of female patients, transumbilical single-port laparoscopic surgery (US-LESS), which integrates the advantages of minimal invasiveness and cosmetic results, has emerged as a novel surgical modality. This surgical approach takes advantage of the natural anatomical features of the umbilicus, leading to a concealed and scarless incision after healing, and thus has achieved high clinical acceptance. However, previous US-LESS hysterectomies were mostly indicated for patients with a uterine size smaller than that of a 12-week gestation. For the hysterectomy of large uteri (uterine size ≥12 weeks of gestation), the surgical difficulty rises drastically due to problems such as limited operative space and narrow visual field. Up to now, there are no clinical guidelines or consensus statements to guide the performance of US-LESS for large uterus hysterectomy. Based on clinical practice, this article systematically summarizes the technical essentials and operative experience of transumbilical single-port laparoscopic hysterectomy for large uteri from the aspects of case selection, preoperative preparation, surgical procedures, intra-operative difficulties and corresponding solutions, postoperative management, as well as prevention and treatment of complications. The purpose is to provide practical references for the standardized clinical application and popularization of US-LESS in large uterus hysterectomy, thereby promoting this surgical modality that combines minimal invasiveness, enhanced recovery and excellent cosmetic effects to better serve patients.