〔Abstract〕 Objective To investigate the effect of heated humidified high-flow nasal cannula (HHFNC) in the treatment of low birth weight infants with neonatal respiratory distress syndrome (NRDS). Methods A total of 60 low birth weight infants with NRDS admitted to the Xiamen Fifth Hospital from March 2019 to July 2020 were selected and divided into two groups according to different treatment regimens: HHFNC group and nasal congestion continuous positive airway pressure (NCPAP) group, with 30 cases in each group. Both groups were given conventional treatment, the HHFNC group was treated with HHFNC, and the NCPAP group was treated with NCPAP. The total effective rate, the incidence of complications and clinical indicators of neonatal treatment in the two groups were observed. Results The total effective rate of treatment in the HHFNC group was 96.67% (29/30), which was higher than 73.33% (22/30) in the NCPAP group, and the difference was statistically significant (P < 0.05). The incidence of nasal injury, air leakage and abdominal distension in the HHFNC group were lower than those in the NCPAP group, and the differences were statistically significant (P < 0.05). The time of non-invasive auxiliary ventilation, milk opening time, invasive auxiliary ventilation time and whole intestine feeding time of neonates in the HHFNC group were shorter than those in the NCPAP group, and the differences were statistically significant (P < 0.05). Conclusion Heating and humidifying nasal catheter high flow ventilation is effective in the treatment of low birth weight NRDS, reducing complications and promoting disease recovery.