The receptor for advanced glycation end products (RAGE) has previously been suggested to stimulate the growth, survival, and metastatic spread of colorectal cancers (CRC). The genetic variant Gly82Ser of RAGE influences its function and is associated with an increased risk of gastric cancer and multiple sclerosis. To investigate the association between the Gly82Ser polymorphisms of RAGE and the risk of CRC, 90 CRC patients and 78 control subjects with benign polyps were genotyped and the results were analyzed using the SPSS statistical software.In comparing with the control group, the CRC group has a higher ratio in the Gly82Ser polymorphism. The odds ratio (OR) for heterozygous GS is 2.037 (95% CI 1.207-3.438); the OR for carriers with the S allele (SS) is 3.32 (95% CI 0.94-11.65). Further stratification analysis of the correlation of the Gly82Ser polymorphism with tumor stages and differentiation indicated that CRC patients with TNM (III + IV) and/or patients with poorly differentiated colorectal cancer have an elevated Gly82Ser polymorphism. The OR for TNM (III + IV) is 3.575, 95% CI 1.495-8.550, and the OR for poorly differentiated is 3.580, 95% CI 1.390-9.217. In conclusion, the RAGE gene Gly82Ser polymorphism may confer not only an increased risk of CRC but also an increased invasion of CRC in the Chinese population.