Background and aim: A skin injury is one of the major neonatal issues. Physicians and nurses reported that skin injuries are one of the most common and serious problems in neonates. The study was aimed to evaluate the effect of skin injury preventive strategy on the neonatal skin condition at neonatal intensive care unit. Subjects and Method: A quasi-experimental research design was used. A purposive sample of sixty neonates was selected from neonatal intensive care unit of El-Monira Pediatric Hospital-Cairo University. Neonates were divided to two groups study and control. Neonatal characteristics were collected by using a structured questionnaire, neonatal skin condition score, and neonatal skin injury risk assessments were used for both groups four times. Neonates in the study group received a designed skin injury prevention strategy for four subsequent days; neonates in the control group only received the hospital routine care. Results: A highly statistical significant difference between total neonatal skins conditions mean score of both groups. A statistical significant correlation in the control and the study groups between gestational age and total NSCS at 4th day as well as there is a statistical significant correlation in the study group between weight and total NSCS at 4th day. Conclusion: skin injury preventive strategy has been shown to be successful in improving neonates' skin conditions, which has a positive effect on critically ill neonates. Recommendation: Skin injury preventive strategy should be applied in all neonatal intensive care units to minimize the hazards associated with skin injuries.