ABSTRACT: The TOB1 (ErbB-2,1) gene is an anti-proliferative factor that has the potential to regulate cell growth and encodes a member of the transducer of erbB-2/B-cell translocation gene protein. The association between the polymorphisms of the TOB1 gene and gastric cancer (GC) risk is still unclear. In this study, 506 GC cases and 548 healthy controls (HCs) were collected to evaluate the association between the eleven SNPs (rs35220381, rs12950561, rs7221352, rs61482741, rs9303568, rs34700818, rs12949115, rs9903822, rs12601477, rs11656976 and rs4626) of the TOB1 gene and GC risk in the population of northeast China. The results showed that there were significant associations of haplotype GCCTTGC, haplotype ATCTTGG, and haplotype GCCACGC with GC risk (P < 0.05, P < 0.001, and P <0.001, respectively). The association between rs12601477 GA+AA genotypes and GC risk was significant among individuals older than 58 (adjusted OR=1.53, 95% CI=1.05-2.22, P< 0.05). The association between rs4626 AG+GG genotypes and GC risk was significant among individuals older than 58 (adjusted OR=1.54, 95% CI = 1.03-2.28, P<0.05). The rs34700818 CT+TT genotypes were associated with a significantly increased risk of T3-T4 (CT+TT vs CC, adjusted OR=1.71, 95% CI= 1.01-2.88, P<0.05) and TNM stage II (CT+TT vs CC, adjusted OR=2.40, 95% CI =1.27-4.52, P<0.01). The rs61482741 CG+GG genotypes were also associated with a significantly increased risk of T3-T4 (CG+GG vs CC, adjusted OR=1.71, 95% CI = 1.01-2.88, P<0.05) and TNM stage II (CG+GG vs CC, adjusted OR=2.40, 95% CI=1.27-4.52, P<0.01). The results suggest that four SNPs (rs12601477, rs4626, rs34700818 and rs61482741) of the TOB1 gene play an important role in the occurrence and development of GC in the Chinese Han population of northeast China.