Background and aim Early detection,diagnosis and treatment of children with congenital heart disease(CHD) has become a hot research issue.The aim of this study was to establish and promote an appropriate technology system for early screening-diagnosis-evaluation of neonatal CHD in the southernmost region of China--Hainan province. Methods From January 1,2019 to December 31,2021,all screening staff from the screening institutions use 2 indicators,namely cardiac auscultation plus pulse oximetry(POX),to screen live newborns within 6 to 72 hours after birth.Diagnosis procedure for the screened-positive newborns was performed in the 31 certified medical institutions,and evaluation procedure for the newborns with confirmed CHD was performed in the 6 certified medical institutions.Data of screening,diagnosis,evaluation and treatment were filled in,uploaded and managed online through a neonatal CHD screening information management net. Results A total of 321,447 live births participated in the CHD screening of this project,providing an overall screening rate of 97.59%(321,447/329,387).And 8,032 cases were screened to be positive.A total of 1099 cases of CHD were confirmed,providing a CHD prevalence of 3.419 per 1000 live births.Atrial septal defect was the most common CHD lesion.The prevalence of insignificant,significant,serious and critical CHD was 1.680,1.260,0.376 and 0.103 per 1000 live births,respectively.The sensitivity of cardiac auscultation,POX and 2 indicators combination(cardiac auscultation plus POX) for CHD detection was 69.15%,33.49% and 91.90%,respectively,and the specificity was 98.36%,99.43% and 97.81%,respectively.The ratio of both positive in 2 indicators in the children with major(serious and critical) CHD at the initial screening was significantly higher than that of single positive in any indicator (χ2=59.455,P<0.001).All children with CHD were evaluated,154 cases of children with major CHD were treated promptly.Only 15 cases of children with major CHD died,the standardized mortality of children aged 0-1 years with CHD was 4.67/100,000,and the case fatality rate of children with major CHD was 9.74%. Conclusions Cardiac auscultation plus POX for CHD screening is non-invasive,simple,easy to operate and reliable,so that it is conducive to be promoted.It is of great significance to promote an appropriate technology for screening,diagnosis and evaluation of neonatal CHD,for which is conducive to timely diagnose and treat children with CHD,especially children with major CHD.