Abstract: 【Abstract】 Objective To discuss the relationship between pregnancy associated plasma protein A (PAPP-A) of second trimester and the levels of free β-human chorionic gonadotropin (β-HCG) and fetal growth restriction (FGR). Methods From June 2017 to June 2019, 3 097 cases of delivery in obstetrics department of People's Hospital of Chengwu County Heze City were selected. According to the FGR diagnostic criteria, 53 cases of FGR were selected as FGR group, and 2 479 cases of single pregnancy pregnant women with normal pregnancy and delivery were selected as control group, and the general data of the two groups were recorded, including: expected delivery age, body mass index (BMI), parity, birth weight,gestational week of delivery. The serum β-HCG was detected by chemiluminescence method. The levelof serum PAPP-A was detected by quantitative enzyme-linked immunosorbent assay; ROC curve line was drawn to evaluate the efficacy of serum β-HCG and PAPP-A levels in diagnosing FGR. Statistical analysis was performed by independent samples t-test and χ2 test. Results There were no significant differences in the expected age, BMI, and parity between the two groups of pregnant women (P>0.05). The gestational weeks(35.8±1.9) and fetal birth weight (2.4±0.3) kg in FGR group were significantly lower than those in control group(39.6±2.0) weeks and (3.6±0.8) kg, which was statistically significant (P<0.05). The serum PAPP-A level of pregnant women in FGR group was lower than that in control group [(0.69±0.20) vs (1.03±0.23) Mom], β-HCG was higher than that of the control group[(0.92±0.27) vs (1.03±0.23) Mom], which was statistically significant (P<0.05). The premature delivery, spontaneous delivery, cesarean section and fetal survival rates in FGR group were 26.42%, 39.62%, 60.38% and 96.23%, which were lower than those in control group by 2.54%, 63.74%, 34.97% and 99.96%. Preterm birth rate, cesarean section rate was higher than the control group, vaginal birth rate, fetal survival rate was lower than the control group, which was statisticallysignificant (P<0.001). Serum β-HCG and PAPP-A levels had a high diagnostic value for FGR. The area under the β-HCG curve was 0.688 (P=0.012), the area under the PAPP-A curve was 0.694 (P<0.001), and the combined detection area under the curve was 0.789 (P<0.001). Conclusion Monitoring serum levels of β-HCG and PAPP-A in the middle of pregnancy has a certain effect on the prediction of FG