Background: The brain damage caused by perinatal hypoxic-ischemic encephalopathy (HIE) can have fatal implications for the baby. Wingless-related integration site (Wnt) signalling is crucial for embryonic cell proliferation, fate determination, and patterning, as Dickkopf-1 (DKK-1) is a secreted protein that plays a role in these processes. Objective: To understand the role of Dkk-1 in the prognosis of newborns with HIE. Patients and Methods: From November 2019 to April 2020, at the neonatal intensive care unit (NICU), Menoufia University Hospitals we undertook a case–control research. Two groups of patients: Asphyxiated 15 newborns were included in patient group (Group 1). Group 2: 15 newborns in good health. Blood count, liver and kidney function test, and blood gas analysis were performed. CT or MRI scans were performed. Serum DDK-1 levels at admission and discharge were measured. Results: In newborns with HIE, the DKK1 level was greater than in normal neonates. DKK-1 level correlated positively with degree of HIE. DKK-1 level correlated positively with worse outcome among HIE neonates. Serum - level >27 µg /L with a sensitivity of 100% and a specificity of 100% for prediction of mortality in the studied HIE neonates. Conclusion: There were association between serum DKK-1 level as diagnostic factor and if an Apgar score was less than 3 at the 5^th minute, pH less than 7.0, or base excess (BE) less than 12 in the venous or cord blood of neonates within 60 minutes of delivery, asphyxia was diagnosed as a prognostic factor in neonates having HIE.