Objective: To explore the effect of targeted nursing on clinical indicators, blood gas analysis indicators and complications in premature neonates using non-invasive ventilator treatment. Methods: A total of 100 premature neonates who received non-invasive ventilator treatment in our hospital from March 2020 to February 2022 were selected as the research objects, and the children were divided into an observation group (n=50) and a control group (n=50) according to the random number table method, targeted nursing and routine nursing interventions were given, respectively, and the clinical indicators, blood gas analysis indicators and the incidence of complications were compared between the two groups. Results: The use time of non-invasive ventilator (3.51±0.47) h and hospital stay (15.24±1.62) d in the observation group were shorter than control group (P<0.05);The arterial partial pressure of oxygen (PaO2) (75.45±7.54) mmHg, PH value (7.42±0.07) and arterial oxygen saturation (SaO2) (98.82±0.56)% in the observation group were higher than those in the control group (69.62±5.96) mmHg , (7.33±0.05), (97.41±1.08)%, arterial blood carbon dioxide partial pressure (PaCO2) (41.63±4.62) mmHg lower than control group (45.59±5.13) mmHg (P<0.05);The incidence of complications in the observation group was 6.00% lower than control group 22.00% (P<0.05). Conclusion: The application of targeted nursing in non-invasive ventilator treatment of premature neonates can shorten the treatment time, improve blood gas analysis indicators, and reduce the risk of complications.