〔Abstract〕 Objective To explore the value of total parenteral nutrition support therapy in the clinical treatment of preterm and critically ill newborns. Methods 86 premature and critically ill newborns treated in Liwan District People's Hospital of Guangzhou from June 2020 to June 2021 were included in this study. They were randomly divided into control group and observation group, with 43 cases in each group. The control group received routine treatment and the observation group received total intravenous nutrition support therapy. The clinical effects of the two groups were compared. Results The total gastrointestinal feeding time, intravenous nutrition time and hospital stay time in the observation group were shorter than those in the control group (P < 0.05). The incidence of complications in the observation group was 25.58%, significantly lower than 53.49% in the control group (P < 0.05). Conclusion Total parenteral nutrition support therapy has good application effect in preterm and critically ill newborns, with high safety and less adverse reactions.