This study aims to comprehensively evaluate and compare the diagnostic accuracy of IL-27 vs. C-reactive protein (CRP) for neonatal sepsis, based on the latest available evidence.<h4>Methods</h4>This systematic review and meta-analysis was conducted following the PRISMA guidelines and prospectively registered in PROSPERO (CRD420251272080). The gene discussed is IL27; the disease is Neonatal sepsis.