Abstract: Objective To investigate the clinical value of genetic screening for early diagnosis of neonatal PTPN11 gene-related Noonan syndrome. Methods We collected neonates with pathogenic variants related to Noonan syndrome in PTPN11 gene from patients of neonatal intensive care unit (NICU) of Children's Hospital of Fudan University enrolled in the Neonatal Genome Project from January 2016 to December 2017 and patients with PTPN11 gene-related Noonan syndrome with neonatal manifestation descriptions from Pubmed, CNKI and Wanfang databases. We summarized their clinical characteristics and gene variants, and compared them with other PTPN11 gene-related Noonan syndrome patients. Results In 5,280 neonates enrolled in the Neonatal Genome Project, there were 21 patients carrying pathogenic variants related to Noonan syndrome in PTPN11 gene, but they cannot fully meet the clinical diagnostic criteria of Noonan syndrome. Combined with 37 cases having neonatal feature descriptions of PTPN11 gene-related Noonan syndrome in published articles, we proposed specific genetic screening indications of neonatal PTPN11 gene-related Noonan syndrome: a. pulmonary stenosis/pulmonary valve stenosis and hypertrophic obstructive cardiomyopathy; b. lymphatic dysplasia-related chylothorax, pleural effusion, unexplained dyspnea; c. thrombocytopenia, leukocytosis, monocytosis; d. cryptorchidism or other genitourinary system abnormality. Conclusion Specific genetic screening indications and diagnosis criteria of neonatal PTPN11 gene-related Noonan syndrome should be established.