Colorectal cancer (CRC) is now regarded as a prevalent cancer worldwide with many contributing risk factors.In this study we tried to find out the relation between the K-Ras proto-oncogene mutation and those risk factors, especially the RBC folic acid level.Eighty CRC patients were examined For RBC folate and mutations codon 12 of K-Ras gene (assayed by enriched RFLP/PCR) and it was found that RBC folic acid (assayed on the immulite 1000 by enzyme chemiluminescence) was significantly deficient in CRC patients with K-Ras (23 patients, mean RBC folate=100.96±51.3 ng/ml) mutation than those without the mutation (57 patients, mean RBC folate=216.6±166.4 ng/ml). Gender also was found to be another predicting risk factor, inspite of being masked by the accentuated folic acid deficiency in females.It was concluded that folic acid supplementation is mandatory, and those at high-risk for CRC should be screened for the risk of K-Ras mutation using the calculation method depending on sex and RBC folate followed by close monitoring for those at high risk for the mutation.