Multiple ligament knee injuries (MLKI) is a serious knee injury that often involves multiple systems and causes severe structural damage to the knee joint. The diagnosis and treatment are still challenging. Recently, with the development of comprehensive researches and minimally invasive techniques, significant progress has been made in the evaluation and treatment of MLKI. However, there are some discrepancies in its diagnosis and treatment, due to the complexity of MLKI, individual variations and limited number of cases. There is no clinical guideline in the diagnosis and treatment of MLKI. In order to summarize the latest advances in its diagnosis and treatment, to help clinicians understand principles in treating MLKI, and to improve the treatment efficacy of MLKI, the Sports Medicine Society of Chinese Research Hospital Association, the Chinese Orthopaedic Association and the Editorial Office of Chinese Journal of Orthopaedics organized domestic experts in the field of knee reconstruction to develop 32 clinical questions and formulate recommendations for MLKI. The clinical practice guideline was developed through evidence summarization, evidence body evaluation and establishment of direction and intensity of recommendations according to the principle of scientificity, practicability and advancement and based on the Grading of Recommendations Assessment, Development and Evaluation approach and the Reporting Items for Practice Guidelines in Healthcare (RIGHT) checklist. The guideline consists of 32 recommendations, with items 1 to 4 regarding the diagnosis of MLKI, items 5 to 23 regarding the treatment and management, items 24 to 27 regarding surgical complications, and items 28 to 32 regarding postoperative rehabilitation. The present guideline aims to improve the standardization of diagnosis and treatment of MLKI in China.