BACKGROUND: The prevalence of obesity is influenced by environmental and genetic factors. Recently, it has been reported that an interaction between genotype and environmental factors can affect each other’s effects on the phenotype. The purpose of this study is to evaluate the recent studies on the fat mass and obesity-associated (FTO) gene interactions with environmental factors affecting on obesity and the impact of these interactions on the success level of the lifestyle intervention. METHODS: All articles published in English from June 1990 to June 2015 were studied. RESULTS: In most studies, the role of the FTO risk alleles for obesity is significantly intensified through reduced physical activity and high calorie diet. Furthermore, the results of studies about the effect of FTO on the success level of lifestyle interventions have been contradictory. Some studies show that FTO genotype influences on the success of lifestyle interventions, while other studies did not report it. CONCLUSION: The results of these studies generally indicate that the effect of the FTO gene on obesity may be influenced by environmental factors and lifestyle. In the other hand, the FTO genotype can affect the success of lifestyle interventions in the prevention and treatment of obesity. Future studies are crucial to elucidate relationships between FTO gene and lifestyle.