Background: Neonatal care places a high priority on preventing and treating neonates with skin breakdown by revising clinical skin care guidelines, developing new techniques, and improvement staff knowledge. The study was aimed to evaluate the effect of an educational program about prevention of skin breakdown on nurses' knowledge in neonatal intensive care units. Subject and method: Research design: A quasiexperimental research design was utilized. Setting: Research was conducted in NICUS at four hospitals affiliated to the Universal Health Insurance Authority (UHIA) in the governorate of Port Said, namely (Al-Hayat -El-Salam -Specialized obstetric -EL-Nasr specialised hospital). Sample: All nurses (70) who were employed in the above settings, along with 50 neonates in each program phase (150) who admitted during the time of data collection. Tools:: Data was gathered using two tools; a structured interviewing questionnaire sheet and Neonatal Skin Condition -Score scale. Results: Findings of the present study revealed statistically significant differences between nurses' knowledge pre & immediate post  (p1),  pre & follow up phase (p2) (p ≤ 0.001),and between  immediate post and follow up phase (p3) (P ≤0.021). Conclusion: The educational program improved nurses' knowledge and as well as decreased skin breakdown in the neonates. Recommendations: Providing nurses with ongoing education and training program about skin breakdown prevention in NICUs.