Objective: To explore the application of Extracorporeal Membrane Oxygenation technology (ECMO) in neonatal respiratory failure and provide guidance for future ECMO technology for critically ill newborns. Methods: Retrospective analysis of the basic data, ECMO support process, and long-term neurological development of nine children supported by ECMO at Zhongshan People’s Hospital from January 2015 to August 2021. Results: From January 2015 to August 2021, the number of admissions to the neonatal department of our hospital was 10,325, with 433 cases of neonatal respiratory failure, which was in line with ECMO support indication of 21 cases, of which 12 were non-ECMO groups and 12 were ECMO groups. In nine cases, the differences in sex, birth weight, gestational age, birth pattern, Apgar score, NCIS score, OI value, hospitalization days, mortality rate, and incidence of intracranial bleeding were not statistically significant (P>0.05). However, the average daily hospitalization cost for children in the ECMO group was significantly higher than that in the non-ECMO group, and the difference was statistically significant (P<0.05). ECMO after 12 h operation, arterial oxygen pressure, and intravenous oxygen saturation are substantially enhanced, while arterial carbon dioxide pressure oxygenation index is considerably reduced, with a statistically significant difference (P<0.05). ECMO pre-operation survival group lactic acid (6.46±2.70) was lower than the death group (17.66±14.62), after operation lactic acid decreased significantly, and after ECMO operation of the death group lactic acid showed an increase in conductivity. During the early stage of ECMO establishment, PT and APTT rapidly rise, while FIB decline. The ACT of both groups of children increased in the early stages of ECMO establishment and then gradually declined. In the ECMO group, seven children survived to discharge, six had no neurological developmental problems, and one had residual neurological sequelae. Conclusion: ECMO can be employed as a complementary supportive treatment for newborns with respiratory failure, and the oxygenation condition can be effectively improved for newborns with respiratory failure who have failed to respond to traditional treatment.