Limited studies about the effects of TLR 4 and IL17 polymorphisms (SNPs) on the risk of colorectal cancer (CRC) have yielded inconsistent results. Totally, 601 CRC patients and 627 controls were enrolled. Unconditional logistic regression was used to estimate the association between tagSNPs and susceptibility of CRC and the interactions effects of gene and environment on the risk of CRC. IL17 rs6973569 AG and AG/AA genotypes significantly decreased the risk of CRC compared with GG genotype (ORadjusted=0.72, 95% CI 0.55-0.94 and ORadjusted=0.74, 95 % CI 0.57-0.97). The haplotype G-T-G-C-A-G accounting for the largest proportion haplotypes increased the risk of CRC (OR=1.27, 95 % CI 1.06-1.53). However, G-C-C-T-A-G and G-C-G-C-A-G haplotypes decreased the susceptibility of CRC. Synergistic interactions between TLR 4 rs1927911 CT/TT and higher pungent food intake as well as IL17 rs6973569 AG/AA genotypes and higher intake of sausage food (ORi=1.72, 95% CI 1.04-2.84 and ORi=3.38, 95% CI 1.28-8.91) on the risk of CRC were observed. IL17 rs6973569 SNP might be an independent factor of susceptibility to CRC. TLR 4 haplotype of G-T-G-C-A-G may increase risk of CRC. Higher intake of pungent and sausage food synergistically interacted with TLR 4 and IL17 SNPs on the risk of CRC.