The aim of the present study was to investigate the associations between adiponectin receptor 2 (AdipoR2) gene polymorphisms, AdipoR2 protein expression levels and the risk of colorectal cancer (CRC). From April 2012 to May 2015, 281 CRC patients (case group) admitted to the China‑Japan Friendship Hospital and 325 healthy control subjects (control group) were recruited for the study. Peripheral venous blood samples were collected and the DNA was extracted. Genotyping was performed using denaturing high‑performance liquid chromatography in the condition of partial degeneration. Linkage disequilibrium and haplotype were analyzed using SHEsis analysis software. AdipoR2 protein expression levels were detected by immunohistochemistry and logistic regression analysis was performed to determine the risk factors of CRC. The distribution of the TT genotype of AdipoR2 rs10773989 and the CC genotype of AdipoR2 rs1044471 was higher in the case group than in the control group (P<0.05). The AdipoR2 rs10773989 polymorphism was associated with the degree of tumor infiltration in CRC (P<0.05) and the AdipoR2 rs1044471 polymorphism was associated with the degree of differentiation and Dukes' staging in CRC (P<0.05). The CT haplotype was identified as a protective factor, while the TC haplotype was a risk factor in a healthy population. AdipoR2 protein expression was associated with the degree of differentiation, Dukes' staging, degree of tumor infiltration and lymphatic metastasis in CRC (all P<0.05). Logistic regression analysis demonstrated that the TT genotype of AdipoR2 rs10773989 and CC genotype of AdipoR2 rs1044471 were independent risk factors for CRC. The AdipoR2 rs10773989 and rs1044471 polymorphisms may be correlated with the susceptibility to CRC. In addition, the TC haplotype and AdipoR2 positive expression may increase the risk of CRC.