Objective: The programmed death-1 (PD-1) is an immunoglobulin gene super family member that renders suppresive effects on T and B cells and strongly inhibits both proliferation and cytokine production. The +7785 C/T SNP (PD-1.5 C/T or + 872, dbSNP rs# cluster id: rs2227981) has been reported to be associated with several autoimmune diseases. Herein, we investigated the association of PD-1.5 C/T SNP with susceptibility and progression of colorectal cancer. Materials and Methods: Two hundred patients with histopathologically confirmed colorectal cancer and 200 age-sex match healthy donors were recruited in the present study. Genomic DNA was extracted from the white blood cells by salting out method and then amplified using Nested polymerase chain reaction-restriction fragment length polymorphism (Nested PCR-RFLP) test. The data analyses were performed using the SPSS software package (version 11.5). Results: The genotype frequencies among both patients and controls indicated no significant deviation from Hardy-Weinberg equilibrium as confirmed by Arlequin 3.1 software package. The frequencies of CC, CT and TT genotypes for the patients and controls were respectively 29.5% vs 37.5%, 54.4% vs 44.5% and 16% vs 18%. The frequency of C and T alleles for the patients and controls were respectively 56.7% vs 59.7% and 43.2% vs 40.3%. Statistical analysis revealed no significant differences in the frequencies of genotype and alleles between patients with colorectal cancer patients, although a trend toward higher occurrence of CT genotype was observed in patients (p=0.057). Our results also discovered no association between the genotypes and the grade of tumor (well differentiated, moderately differentiated and poorly differentiated) (p=.63). Conclusion: Current study revealed no association between this SNP with susceptibility to colorectal cancer in Iranian population. Our previous studies from the same population indicated the association of PD-1.5 C/T with susceptibility to head and neck cancer, but not breast cancer.