||Susceptibility to colorectal cancer (CRC) and breast cancer has been associated with environmental and dietary risk factors, such as heterocyclic amine carcinogens, and polycyclic aromatic hydrocarbons. Cytochrome P450 2C19 (CYP2C19) is one of the Phase I xenobiotics metabolic enzyme (XME) responsible for the metabolism and disposition of many xenobiotics. AhR is a transcriptional factor upregulating the expression of several XMEs. In this study, associations between the genetic polymorphisms of the CYP2C19 gene and AHR gene with CRC and breast cancer were investigated among Han Chinese using case-control studies. Two hundreds CRC patients, 311 breast cancer patients and 380 healthy controls were genotyped to detect single nucleotide polymorphism (SNP). For CYP2C19, SNP rs3758581 was significant associated with the CRC (p<0.05) in both sexes. Its odds ratio is 2.8675 (95%CI 1.3294 - 6.1848) in male and 3.2795 (95%CI1.29 - 8.3048) in female. One haplotype GGATA showed p value smaller than 0.05 in the male group of CRC samples. No association was found for breast cancer. For AHR, SNPs rs7796976 and rs2066853 showed a statistically significant (p<0.05) correlation with CRC in male. SNP rs2066853 also showed a statistically significant (p<0.05) correlation with breast cancer. SNP rs7796976 had an odds ratio 0.4994 (95% CI 0.3371 - 0.7401) in male CRC sample and 0.8608 (95% CI 0.5068 - 1.4621) in breast cancer sample indicating the minor allele carriers are protected from both CRC and breast cancer. SNP rs2066853 had an odds ratio 1.4537 (95% CI 1.0768 - 1.9625) in male CRC sample. Two haplotypes G-A and A-G got a p value smaller than 0.05 in the male CRC samples showed a correlation with CRC.