Objective To explore the application of axillary vein indwelling needle technique in premature infant of neonatal intensive care unit (NICU). Methods A total of 110 cases of NICU premature infants admitted to our hospital from June to December 2019 were selected as the research objects, they were divided into study group and control group using random number table method, 55 cases in each group. The study group received intravenous indwelling trocar infusion, and the control group received intravenous infusion of extremities and scalp. The effect of needle placement, indwelling time and the incidence of related complications were compared between the two groups. Results The success rate of first needle puncture in the study group was higher than that in the control group, the puncture time was shorter than that in the control group, the unplanned extubation rate was lower than that in the control group, the differences were statistically significant (P＜0.05). There was no significant difference in the accidental drop-off rate of the indwelling needle between the two groups (P＞0.05). The proportion of indwelling needle retention time>72 h in the study group was higher than that in the control group, and the indwelling time was longer than that in the control group,the differences were statistically significant (P＜0.05). The total incidence of complications in the study group was lower than that in the control group, the difference was statistically significant (P＜0.05). Conclusion The technique of axillary vein indwelling needle can effectively improve the effect of NICU neonates and reduce the incidence of complications,it is worthy of further clinical application.