Background: Nasal continuous positive airway pressure (NCPAP) is an effective method of ventilation in newborns with respiratory distress syndrome (RDS). Using an appropriate nasal skin care protocol is identical to prevention or reduction of nasal skin breakdown in those who receive NCPAP. This study aimed to investigate the effectiveness of an evidence-based clinical care protocol on nasal skin integrity in preterm newborns who receive NCPAP. Materials and Methods: A Randomized Controlled Trial was used to conduct the study. A cohort of 110 preterm newborns with a gestational age (GA) of 25 to 36 weeks, receiving nasal continuous positive airway pressure (NCPAP) for RDS in the neonatal intensive care unit of a university teaching hospital were selected to perform the study. They were randomly assigned to a protocolized nasal skin care (group A) or to a group receiving the routine care (group B). Nasal skin integrity of the preterm neonates, were measured on a daily basis for 10 days using the Neonatal Skin Condition Scale (NSCS) 24 hours after placement of NCPAPs in both groups. Results: Each intervention and control group included 55 neonates. 65.50% of neonates in the control group and 47.30% of neonates in the intervention group were male. Repeated measures analysis showed that NSCS scores were significantly lower in intervention group receiving nasal skin care in accordance with the protocol than the control group receiving the routine nasal skin care (P= 0.000). Conclusion: In this study, the protocolized care reduced nasal skin breakdown in the preterm newborns receiving NCPAP. Therefore, it can be used as an effective method in nasal skin care in neonates who are treated by NCPAP.