Objective: To study the relationship between rs1136410 polymorphism in poly (ADP-ribose) polymerase-1 gene (PARP-1) with obesity and non-alcoholic fatty liver disease (NAFLD) in children and adolescents, and to provide a reference for demonstrating the mechanism of obesity and NAFLD of children and adolescents and making the early prevention strategies. Methods: In total, 2 030 children and adolescents aged 7-18 years old were recruited. Anthropometric measurements were performed. Liver B-ultrasound detection were performed in a subgroup. The matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TDF MS) was used for genotyping the rs1136410 polymorphism. Logistic regression was used to analyze the relationship between rs1136410 polymorphism and obesity or NAFLD in children and adolescents. Results: Totally, 1 325 subjects were in non-obese group and 705 subjects were in obese group. The frequency of G allele and A allele were 43.86% and 56.14%. After adjusting for gender, age, and study population, the risk of obesity increased by 1.17 times for each additional A allele of rs1136410 polymorphism(OR=1.17, 95%CI=1.02-1.33, P=0.03). And the risk of NAFLD increased by 1.43 times for each additional A allele of rs1136410 polymorphism(OR=1.43, 95%CI=1.11-1.85, P=0.01). After further adjustment for BMI, rs1136410 polymorphism was not associated with NAFLD(P=0.70). Conclusion The rs1136410 polymorphism in PARP-1 gene is associated with obesity and NAFLD in children and adolescents. The effect of the gene polymorphism on NAFLD is mediated by BMI.