The aim of the present study was to determine the association of the Forkhead box P3 (FoxP3) rs3761548 polymorphism with the risk of colorectal cancer (CRC). Polymorphism genotyping was detected with polymerase chain reaction-polyacrylamide gel electrophoresis (PCR-PAGE), and data revealed that the AA, AC, and the combined A variant genotype (AA+AC) conferred a significantly greater risk of CRC [OR (95% CI) = 2.806 (1.726-4.563), 1.54 (1.121-2.11), and 1.797 (1.344-2.404), respectively]. Moreover, the A allele of rs3761548 was observed to be associated with higher susceptibility of CRC [OR (95% CI) = 1.792 (1.424-2.254)]. Unfortunately, no significant association was observed between the two subgroups after stratification by clinical characteristics including age; gender; tumor size, growth pattern, or differentiation; lymph node metastasis; and TNM pathological stage. Thus, we concluded that the FoxP3 gene polymorphism contributes to CRC susceptibility in a Chinese population.