Background: High perianal abscess is an emergency in the anorectal department. It can result in long-term pain and a huge psychological burden to patients, and seriously affects the quality of life of patients. At present, the effect of antibiotics alone for high perianal abscess is not satisfactory. Loose combined cutting seton (LCCS) can effectively treat high anal fistulas and high perianal abscesses in our clinical practice, but there is no sufficient evidence for its effectiveness in the treatment of high perianal abscesses. The purpose of this study is to observe the effectiveness and safety of LCCS in the treatment of high perianal abscess. Methods: This study is a single-center, prospective, single-blind, randomized, controlled, non-inferiority clinical study. This study will include patients who are diagnosed with high perianal abscesses and hospitalized for surgery in the Department of Proctology in China-Japan Friendship Hospital (enrollment time: from January 2022 through December 2024). Patients in the experimental group will be treated with LCCS, while patients in the control group will be treated with incision and drainage. Follow-ups will be performed at 1, 3, 7, 14, 21, 28, 90, and 180 days after the operation. The main outcome measures are as follows: (I) cure rate; (II) half-year recurrence rate; (III) postoperative pain visual analog scale (VAS) score; (IV) wound healing time; (V) postoperative anal function evaluation by the Wexner scale; (VI) pressure measurement of the anal canal and rectum before and at half a year after surgery; and (VII) the incidence of adverse events. Discussion: This study will assess the effectiveness and safety of LCCS in the treatment of high perianal abscess through a strictly designed randomized controlled study, and provides evidence for treatment in clinical practice, thereby improving the treatment effect and improving patients' quality of life.