【Objective】 To analyze ABO system hemolytic disease of the fetus and newborn (HDFN) and its influencing factors in Obstetrics Department of our hospital. 【Methods】 The blood samples of 1 040 neonates and their mothers in the obstetric department of our hospital were retrospectively analyzed from September 2022 to January 2023, including ABO and RhD blood group of the neonates and mothers, as well as 3 tests of HDFN, Hb, total bilirubin (TBIL) and indirect bilirubin(IBIL) of the neonates. Relevant clinical data of the neonates and mothers were collected, including maternal and neonatal age, neonatal sex, maternal pregnancy history, gestational age and delivery mode, and their influences on ABO-HDFN were analyzed. 【Results】 Among 1 040 HDFN samples, 298 were ABO incompatibility, among which 113 were HDFN positive, with a positive rate of 37.9% (113/298); the positive rate of HDFN in neonates born to mothers with type O was significantly higher than that in neonates born to mothers with type A and B (71.4% vs 8.2%, P<0.05); the positive rate of HDFN in neonates with antigen-A incompatibility was significantly higher than that in neonates with antigen-B incompatibility (48.7%vs 26.7%, P<0.05), which was the highest in neonates with O-A incompatibility [83.6% (61/73)], followed by O-B incompatibility [58.2% (39/67)]. There was no significant difference in Hb and bilirubin among the other groups except for the difference of Hb between the O-A incompatibility HDFN positive group and the HDFN negative group [(145.0±16.0) vs(153.4±13.2), P<0.05)]. The levels of Hb, TBIL and IBIL in the "direct antiglobulin test+ indirect antiglobulin test+release test+" group were significantly different from those in the HDFN negative group[(144.9±21.6) vs (153.3±13.2), P <0.05; (36.9±11.8) vs (29.6±6.1), P<0.05; (30.6±12.7) vs (23.0±6.9), P<0.05, respectively]. Logistic regression analysis showed that maternal delivery frequency, mother-neonate incompatible antigen and maternal blood type were independent risk factors for HDFN. 【Conclusion】 ABO-HDFN occurred mainly in neonates born to O-type mothers, and the positive rate was the highest in neonates with O-A incompatibility. The severity of HDFN had little relationship with the mother-neonate blood type, but had relationship with the result of 3 tests of HDFN. Maternal delivery frequency, mother-neonate incompatible antigen and maternal blood type were independent risk factors for HDFN.