Summary Background PNPLA3 I148M polymorphism has an effect on modulation of estimated glomerular filtration rate (eGFR) in nonobese nondiabetic adults and in children with histologically confirmed nonalcoholic fatty liver disease (NAFLD). Objectives The objective of the study is to explore the impact of PNPLA3 I148M polymorphism on eGFR in children with obesity with and without NAFLD. Methods We genotyped 591 patients with obesity for PNPLA3 I148M polymorphism. Anthropometrical, biochemical, and instrumental data were collected. NAFLD was defined by the presence of ultrasound‐detected liver steatosis and/or ALT levels greater than 40 IU/L. Results Patients with NAFLD showed significantly lower eGFR levels compared with subjects without NAFLD. Children with PNPLA3 MM genotype showed lower eGFR levels compared with those with either PNPLA3 IM or II genotypes both in the presence and absence of NAFLD. A general linear model for eGFR variance, including gender, duration of obesity, PNPLA3 genotypes, HOMA, BMI‐SDS, LDL‐C, and triglycerides as covariates, confirmed an inverse association between eGFR and PNPLA3 genotype only in the presence of NAFLD. Conclusions Children with obesity and PNPLA3 MM genotype show lower eGFR levels compared with other genotypes, with a major effect of this polymorphism in the presence of NAFLD.