Epidermal growth factor (EGF) plays an important role in tumorigenesis. The association between the +61 A/G polymorphism of the EGF gene and colon cancer risk remains controversial and unclear. The objective of this study was to investigate the association between EGF +61 A/G polymorphism and colon cancer risk in a Chinese population. A hospital-based case-control study was conducted to assess the possible association between EGF +61 A/G polymorphism and colon cancer risk. A total of 180 colon cancer patients and 180 cancer-free healthy controls were recruited in the Chinese population. Genomic DNA was isolated from peripheral blood, and gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Colon cancer patients had a significantly higher frequency of +61 GG genotype (odds ratio [OR] = 1.93, 95% confidence interval [CI] = 1.07, 3.50; p = 0.03) than that of controls. When stratified by the tumor location, tumor size, growth pattern, differentiation, and tumor-node-metastasis (TNM) stage of colon cancer, no statistically significant results were observed. Our study revealed that EGF +61 GG genotype was associated with a higher risk of colon cancer in the Chinese population.