MicroRNA (miRNA) related genetic variation may change miRNA binding affinity and mRNA expression levels of the target genes, thus leading to altered metabolic parameters. This study explored the influence of let-7 related single nucleotide polymorphisms (SNPs) on individual susceptibility to metabolic syndrome (MetS) in a Chinese population. Seven SNPs located at the pri-let-7 gene region, pre-let-7 gene region or 3'-UTR of the KRAS gene were selected. The SNPs were genotyped in 503 MetS patients and 529 normal controls using the high-throughput Sequenom genotyping platform. Unconditional logistic regression analysis was utilized to estimate the association between these SNPs and the risk of MetS. There are three SNPs significantly associated with MetS. The A allele of rs17276588 was associated with an increased risk effect for MetS (Adjusted OR=1.75, 95%CI 1.37-2.25, P<0.001). Rs10993081 AG genotype was significantly associated with an increased risk of MetS compared with AA genotypes (Adjusted OR=1.42, 95%CI 1.11-1.83, P=0.006). Rs10877887 TC genotype was significantly associated with an increased risk of MetS compared with TT genotypes (Adjusted OR=1.52, 95% CI 1.16-1.99, P=0.002). Additionally, interactions between rs7045890 and rs712, rs17276588 and rs10877887 were significantly associated with risk of MetS. In conclusion, our study found that let-7 related genetic variation is associated with MetS and may contribute to the susceptibility of MetS. Larger, prospective studies are warranted to validate our findings.