Objective: To explore the application value of FOCUS-PDCA model in the safety management of peripherally inserted central catheter (PICC) catheterization for premature infants. Methods: Clinical data of 75 premature infants who received PICC catheterization in NICU of our hospital from April 2018 to October 2020 were retrospectively analyzed. A total of 37 premature infants who received routine nursing measures were included in a control group, and 38 premature infants who received FOCUS-PDCA model nursing were included in an observation group. The incidence rates of PICC catheterization complications, one-time puncture success rate, compliance, PICC indwelling time, hospital stay and psychological stress response were compared between the 2 groups, and the family satisfaction was recorded. Results: The total incidence rate of PICC catheterization complications of premature infants in the observation group was lower than that in the control group while the one-time puncture success rate and compliance were higher than those in the control group, and the PICC indwelling time was longer than that in the control group while hospital stay was shorter than that in the control group (all P<0.05). After successful PICC catheterization, the systolic blood pressure, diastolic blood pressure and heart rate of premature infants in the observation group were lower than those in the control group (all P<0.05). The satisfaction rate and satisfaction score of the family members in the observation group were higher than those in the control group (all P<0.05). Conclusion: FOCUS-PDCA model in the nursing of premature infants can significantly reduce the occurrence of PICC catheterization complications, lower the psychological stress response during catheterization, improve the one-time catheterization success rate and compliance, and improve the family satisfaction.