Objective: To examine the prospective effect of cesarean section on pubertal development after controlling the polygenic susceptibility for early puberty in boys and girls,and to provide a reference for choosing a delivervary way beneficial to pubertal development. Methods: Cluster sampling method was used to select 997 students of grade 1 to 3 from 2 priwary schools in Bengbu of Anhui in 2016 to establish the puberty development cohort. Delivery mode,birth weight,gestational age,early teeding way,family income and parental educational background were derived from parental questionnaire. Breast Tanner stage and testicular volume of 997 children were annually assessed. The polygenic risk score (PRS) was computed based on 17 SNPs derived from published genome-wide association studies for early pubertal timing. Kaplan-Meier analyses was used to examine associations between cesarean section with pubertal development in boys and girls. Results: The average age of 997 children was 8.01±0.84 years old, and average BMI was (17.96±2.96) kg/m2. The prevalence of cesarean section for boys and girls was 43.30% and 32.47%, respectively. At baseline, the detection of thelarche in girls delivered by cesarean section (39.89%) was higher than that of girls delivered naturally (4.39%) (χ2=118.65, P<0.01). Similar result was observed during the last follow-up, the detection of thelarche in girls born by cesarean section (95.21%) was higher than girls born vaginally (68.48%), respectively (χ2=51.42, P<0.01). After adjusting for confounding factors (age, BMI, birthweight, infancy feeding, gestational age, household monthly income and parental education), girls delivered by cesarean section had maturation at significantly younger than girls who delivered naturally (Hazard Ratio, HR=1.98，95%CI=1.67-2.34，P<0.01). Conclusion Caesarean section might increase the risk of earlier age at pubertal onset in a sex-specific manner. Whether natural delivery could be one of the protective measures to prevent early pubertal timing in children warrants further investigation.