Background: CDKN1A (p21(WAF1/CIP1)) plays an important role in cell cycle regulation. Somatic alterations in genes which regulate cell division have been shown to be related to different types of cancer prognosis and survival. The purpose of this study was to investigate the effect of the CDKN1A Ser31Arg and C20T gene polymorphisms in Turkish patients with colorectal cancer. Patients and Methods: CDKN1A Ser/Arg and C20T polymorphisms were studied in 53 patients with colorectal cancer and 64 healthy controls. Genomic DNA was amplified by polymerase chain reaction (PCR) and genotypes were determinated by the restriction fragment length polymorphism (RFLP) method. Results: There were statistically significant differences in the distribution of CDKN1A Ser/Arg genotypes and allele frequencies between colorectal cancer patients and healthy controls (p=0.040 and p=0.01, respectively). CDKN1A C20T genotype frequency did not show any significant differences between patients and controls. We combined the results for C20T and Ser31Arg polymorphisms and observed that a lower risk of colorectal cancer was associated with CT/SerArg combined genotypes compared to controls and this difference was statistically significant (p=0.024; odds ratio (OR)=0.322, 95% confidence interval (CI)=0.114-0.912). C20T C allele and SerSer genotypes significantly increased risk compared to other combined genotypes (p=0.034; OR=1.265, 95% CI=1.020-1.569). Conclusion: The results of present study demonstrated that, potentially. CDKN1A functional polymorphisms may contribute to the risk of colorectal cancer in Turkish.