The association of rs10818488 SNP located in TRAF1/C5 region with Rheumatoid Arthritis (RA), has been picked up by genome-wide association studies. Independent studies in different populations revealed inconsistent results. The aim of this study was to investigate the possible association of this SNP with RA in Iranian population. A total of 362 cases and 422 healthy controls were recruited in this study. Genomic DNA was extracted from whole blood and the genotyping was performed by PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism). A set of genotypes was confirmed by sequencing. Genotype and allele frequencies were compared between the case and control groups. Analysis indicated a higher frequency of A allele in cases, although the difference was not statistically significant (Chi-square=2.8, p=0.09). Comparison of genotype frequencies, revealed higher frequencies of AA and AG genotypes in case group but statistically the difference was not significant (Chi-square=2.72, p=0.25). These findings suggest that the rs0818488 in TRAF1/C5 region is not associated with rheumatoid arthritis in Iranian population.