Objective To develop a multidisciplinary nursing program for Prader-Willi syndrome with spinal deformity and evaluate its effectiveness in clinical practice. Methods In July 2016, a multidisciplinary collaborative team was established before the treatment of children with Prader-Willi syndrome complicated with spinal deformity. For the nursing difficulties in the perioperative period, relevant literature was consulted, and a multidisciplinary collaborative nursing plan was formulated, which included nutrition management and blood glucose control, management of obstructive sleep apnea hypopnea syndrome, behavioral intervention related to mental change, and early identification and management of complications. The developed multidisciplinary collaborative nursing program was applied to three children with Prader-Willi syndrome complicated with spinal deformity in Peking Union Medical College Hospital from July 2016 to October 2018, and their postoperative recovery was evaluated. Results One child had inguinal skin ulceration when admitted to hospital, which was significantly improved after active treatment. The perioperative blood glucose level control of the three children was satisfactory, and there was no postoperative gastrointestinal dysfunction, deep wound infection, respiratory complications, internal fixation failure or other complications, and no asphyxia, fall, loss, or other adverse events. The follow-up compliance after discharge was 100%. Conclusions Multidisciplinary collaboration programs can escort patient’ safety and promote their recovery, improve the professional level of nursing staff, and reflect the nursing value. As a working mode, it can be further popularized and used for reference in the nursing of other difficult diseases.