Objective To summarize the best evidence on cardiopulmonary resuscitation（CPR） in the prone position with invasive mechanical ventilation. Methods A systematic literature search was conducted in both domestic and foreign clinical decision support systems, databases as well as relevant professional or guideline websites for clinical decision-making, evidence summaries，guidelines, expert consensuses，and systematic reviews on CPR in the prone position with invasive mechanical ventilation. The time limit of searching was set from the date of database’s inception to November 2023. The researchers screened the literature，extracted the data, evaluated the quality of the included literature，and afterward，extracted, integrated，and graded the evidence. Results A total of eight studies were included, consisting of four guidelines, one systematic reviews, and three expert consensuses. In addition, 18 pieces of evidence were synthesized into five categories, which including position selection, resuscitation preparation, compression points，defibrillation preparation，and resuscitation monitoring. Conclusion This study summarizes the best evidence for performing CPR in the prone position with invasive mechanical ventilation. Medical staff should carefully select and apply evidence and carry out clinical practice based on clinical situation and professional judgment.