Objective To investigate the correlations of fat mass and obesity associated (FTO)- rs9930506 polymorphism with cognitive deficit and occurrence of type 2 diabetes (T2DM). Methods Totally 450 T2DM patients hospitalized in Tangshan Gongren Hospital from March 2008 to March 2010 were enrolled as the patient group, and 512 persons without T2DM were collected from a community in Beijing at the same period as the control group. RBANS was used to evaluate cognitive performance. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was applied to explore FTO-rs9930506 polymorphism. Results There was no significant difference either in allele distribution or genotype frequencies of FTO-rs9930506 locus between the patient and control groups (P > 0.05). However, significant difference was found in allele distribution between the female subjects of the two groups (P < 0.05); moreover, the subjects with G allele had 1.464 times higher risk to develop T2DM than the A allele carriers. Furhermore, BMI of the GG genotype carriers was higher than that of the AA and AG genotype carriers (P < 0.05), the language capability and delayed memory of the GG genotype carriers were worse than those of the AA and AG genotype carriers (P < 0.05). Conclusions G allele of FTO-rs9930506 locus is a risk allele for female to develop T2DM. FTO-rs9930506 polymorphism plays a role in cognitive deficit of the patients with T2DM.