Necrotizing enterocolitis (NEC) is a devastating gastrointestinal condition mainly affecting premature infants, and gasdermin D (GSDMD) has emerged as a molecule of interest due to its pivotal role in the inflammatory process called pyroptosis in NEC pathogenesis. The aim of this study is to examine the potential of GSDMD and interleukin-1β (IL-1β) as early diagnostic biomarkers for NEC.We examined 207 infants with clinical symptoms of NEC admitted to our neonatal intensive care unit (NICU) between December 2023 and June 2024. After excluding those with congenital gastrointestinal diseases and other factors, 180 infants were included in the study. Among these, 59 were confirmed to have NEC according to Bell Stage II criteria, and 56 matched controls were selected through propensity score matching (PSM). Blood samples were analyzed for GSDMD expression using quantitative polymerase chain reaction (qPCR) and for IL-1β levels using enzyme-linked immunosorbent assay (ELISA).Patients with NEC exhibited significantly elevated levels of GSDMD (18.46±8.58) and IL-1β (9.05±3.42) compared to controls. Receiver operating characteristic (ROC) curve analysis indicated that GSDMD had a higher predictive value for NEC with an area under the curve (AUC) of 0.83 than IL-1β (AUC 0.77). Clinical symptoms such as fatigue, abdominal distention, and reduced bowel sounds were significantly more common in patients with NEC. Laboratory results showed lower neutrophil and red blood cell counts, higher platelet counts, and increased levels of C-reactive protein (CRP) and procalcitonin (PCT) in patients with NEC.GSDMD and IL-1β can serve as valuable biomarkers for the early diagnosis of NEC, providing insights into the disease's pathogenesis and facilitating improved strategies for early detection and intervention.2024 AME Publishing Company. All rights reserved.