A case-control study was carried out to examine the relation between genetic polymorphisms of five genes, cigarette smoking and colorectal cancer risk. We collected blood samples from 106 colorectal cancer patients and 100 healthy persons, then analyzed them to identify genotypes for glutathione S-transferase (GST) M1, T1, P1, N-acetyltransferase (NAT) 1 and 2 by the PCR method. We also collected smoking history data from all participants by questionnaire. From statistical evaluation on various combinations of genotypes, we observed that the cancer risk of those who have both GSTM1 present genotype and GSTP1 Adenine/Adenine homozygous genotype was significantly less than those who have other combinations of genotypes for two genes. For other combinations of genes, there was no significant association between genotype and cancer risk. There was also no significant association between amount of cigarette smoking and the cancer risk. These findings suggest that it is valuable to study cancer risk when examining genotypes of more than two genes at the same time. For further study, we need to collect more samples to increase statistical reliability, and besides cigarette smoking, include the nutrition data as an environmental factor.