Abstract: Objective To explore the application and nursing of peripherally inserted central catheter(PICC)in Neonatal Intensive Care Unit(NICU). Methods Totally 94 neonates with PICC in NICU were selected and randomly divided into control group and study group, with 47 cases in each group. The control group was conducted with routine nursing measures, and the study group was conducted with comprehensive nursing measures on the basis of the control group. The complications related to PICC catheterization, the success rate of catheterization by one time, the incidence of unplanned extubation and the nursing satisfaction degree of neonatal family members were compared between the two groups. Results The success rate of one-time catheterization and the total satisfaction degree of neonatal family members to nursing service in the study group were significantly higher than those in the control group, while the incidence rates of unplanned extubation and PICC related complications in the study group were significantly lower than those in the control group(P<0.05). Conclusion Application of PICC catheterization combined with comprehensive nursing measures can effectively reduce the incidence rate of complications in NICU newborns, ensure the catheterization effect, and increase the nursing satisfaction degree of neonatal family members.