The aim of the study was to investigate whether lifestyle factors modify the association between fat mass and obesity-associated(FTO)gene single nucleotide polymorphisms (SNPs) and obesity in a Turkish population. The study included 400 unrelated individuals, aged 24-50 years recruited in a hospital setting. Dietary intake and physical activity were assessed using 24-hour dietary recall and self-report questionnaire, respectively. A genetic risk score (GRS) was developed usingFTOSNPs, rs9939609 and rs10163409. Body mass index and fat mass index were significantly associated withFTOSNP rs9939609 (p = 0.001 andp = 0.002, respectively) and GRS (p = 0.002 andp = 0.003, respectively). The interactions between SNP rs9939609 and physical activity on adiponectin concentrations, and SNP rs10163409 and dietary protein intake on increased waist circumference were statistically significant (P-interaction = 0.027 andP(interaction) = 0.044, respectively). Our study has demonstrated that the association betweenFTOSNPs and central obesity might be modified by lifestyle factors in this Turkish population.