Colorectal cancer has been considered as one of the complicated multi-stage processes after adenoma-carcinoma sequence. Therefore, studies of the molecular dysregulation basis could present information on the recognition of the potent biomarkers and treatment targets for this disease. Even though outcomes of the patients with colorectal cancer have been improved largely with current annual screening plans, it is necessary to have reliable prognostic biomarkers because of the disease heterogeneity. There is a significant relationship between SNP in IL1RN* 2 (IL1ra), −509 C/T (TGFB1), rs11556218 T>G and rs4778889 T/C (IL16), miRNA-binding site polymorphisms in IL16, rs4464148 (SMAD7), rs6983267 (EGF), GSTT1, TACG haplotype (CTLA4), 1793G> A (MTHFR), Leu/Leu genotype of (EXO1), −137 G/C (IL18), C/T genotype (XRCC3), I3434T (XRCC7), MGMT, C3435T (MDR1), ff genotype of FokI, 677CT+TT (MTHFR), G2677T/A (MDR1) and CRC. Increased risk has been observed in VDR ApaI genotype "aa". Finally, the protective effect has been explored in the TACA haplotype (CTLA4). According to the findings, the genetic polymorphisms in the immunity-associated genes are related to the CRC amongst the Iranian patients. Therefore, more large-scale functional investigations are necessary for confirming the results.