Background/Aims: IGF-1 can act as an endocrine hormone and its signaling server as essential roles in regulating tumorigenesis. Polymorphisms in IGF-1 have been reported associated bad prognosis of with human cancer, but their association with the risk of human gastric cancer (GC) has not been found so far. In this study rs6218 located in the 3'UTR of IGF-1 was selected to evaluate its relationship with the risk of GC among Chinese population. Methods: Questionnaire, SNaPshot genotype assay, real time PCR assay, cell transfection and the dual luciferase reporter assay were used in our study. Results: SNP rs6218 in IGF-1 3'-UTR was involved in the occurrence of GC by acting as a tumor promotion factor while rs6128 acting as a risk factor. SNP rs6128 was also could be regulated by miR-603 which caused an up-regulation of IGF-1 in patients with UC and CC genotype. Furthermore, the carriers of UC and CC genotype presented a big tumor size as well as the high probability of metastasis. Conclusion: In conclusion, our findings have shown that the SNP rs6218 in IGF-1 3'-UTR, through disrupting the regulatory role of miR-603 in IGF-1 expression, rs16128 in IGF-1 might act as a promotion factor in the pathogenesis of GC.