〔Abstract〕 To explore the association between mammalian sterile 20-like kinase 2 (MST2) gene polymorphism and haplotype and the risk of colorectal cancer, rectal cancer, and colon cancer in the Han population in Baotou area by case-control association study. Methods A total of 390 patients with colorectal cancer diagnosed by pathology and 413 normal physical examination pop- ulation were collected, and 2 mL of peripheral blood was taken for subsequent gene genotyping. Single nucleotide polymorphisms (SNPs) of MST2 gene were screened according to the genetic polymorphism data of Chinese Han population provided by the NCBI-Hapmap database. Gene genotyping was performed by Taqman method. Logistic regression was used to calculate the association between each SNP and the risk of colorectal cancer, colon cancer, and rectal cancer under codominant, dominant, overdominant, and recessive genetic models. Results Five SNPs ofMST2 gene were screened, namely rs11783149, rs10955176, rs7827435, rs4075986, rs3019295. Among them, SNP rs4075986 was associated with the risk of colorectal cancer. Compared with the rs4075986 GG+AA genotype, carrying the AG genotype [OR(95%CI)=2.473(1.844- 3.316) could increase the risk of colorectal cancer. Compared with the rs4075986 GG genotype, carrying the AG genotype [OR(95%CI)=2.475 (1.844-3.323) could increase the risk of colorectal cancer. SNP rs4075986 and rs3019295 were associated with the risk of rectal cancer. Compared with the rs4075986 GG+AA genotype, carrying the AG genotype [OR(95%CI)=3.411 (2.387-4.874)] could increase the risk of rectal cancer .Compared with the GG genotype, carrying the AG+AA genotype[OR(95% CI)=1.824 (1.262-2.638)] could increase the risk of rectal cancer. Compared with the rs3019295 GG+AA genotype, carrying the AG genotype [OR(95% CI)=0.706(0.501-0.996)] could reduce the risk of rectal cancer . SNP rs11783149 and rs4075986 were associated with the risk of colon cancer.Compared with the rs11783149 CC genotype, carrying the TT [OR(95%CI)=10.883(1.186-99.862)] and CT [OR(95%CI)=1.665(1.036-2.675)] genotype could increase the risk of colon cancer, respectively. Compared with the rs4075986 GG genotype, the AG+AA genotype [OR(95%CI)= 1.824(1.262-2.638)] could increase the risk of colon cancer. Conclusion MST2 gene SNP rs3019295 AG genotype may be protective factor for rectal cancer. SNP rs11783149 CT and TT genotypes maybe risk factors for colon cancer. SNP rs4075986 AG and AG+AA genotypes may be a common risk factors for colorectal cancer, rectal cancer and colon cancer.