Objective: To explore clinical risk factors of neonatal asphyxia and to provide evidence for prevention of neonatal asphyxia. Methods: Clinical data of singleton live births and their mothers in the Maternal and Child Health Hospital of Anhui Medical University from January 2018 to December 2019 were retrospectively analyzed. The newborns with asphyxia were taken as an observation group. According to the proportion of 1:2, non-asphyxiated newborns delivered by mothers with adjacent hospitalization numbers were selected as a control group. The clinical data of newborns and mothers of the 2 groups were compared, and the related clinical risk factors of neonatal asphyxia were analyzed. The data were analyzed by t-test, χ2 test and binomial logistic regression analysis and multivariate logistic regression analysis. Results: The incidence of neonatal asphyxia in our hospital was 0.85% (246/29 000). There were significant differences in hypertensive disorder of pregnancy, intrahepatic cholestasis of pregnancy, fever during delivery, fetal distress, abnormal amniotic fluid, placental abnormality, parturient, prenatal planned delivery, cesarean section, forceps delivery, prolonged second stage of labor, abnormal umbilical cord, and preterm delivery of mothers between the 2 groups (P<0.05). Multivariate logistic regression analysis showed that intrahepatic cholestasis of pregnancy, abnormal fetal position, fever during delivery, abnormal amniotic fluid, abnormal umbilical cord, placental abnormality, preterm delivery, and fetal distress were relevant clinical risk factors of neonatal asphyxia. Conclusion: Intrahepatic cholestasis of pregnancy, abnormal fetal position, fever during delivery, abnormal amniotic fluid, abnormal umbilical cord, placental abnormality, premature delivery, and fetal distress are the relevant clinical risk factors of neonatal asphyxia. Management of high risk groups should be strengthened to reduce the incidence of neonatal asphyxia.