Abstract Growing data supported that epigenetic modifications, including altered DNA methylation have a potential role in the pathogenesis of autoimmune thyroid diseases (AITD). In the present study we aimed to investigate the methylation status of ICAM-1 gene promoter in patients with AITD. Forty patients with Graves’ disease (GD), 40 patients with Hashimoto thyroiditis (HT) and 40 normal controls were included. DNA extraction from blood samples was done to analyze the ICAM- 1 methylation status using methylation-specific PCR method. RNA was also extracted to determine the ICAM-1 expression values by real time PCR. We found that the differences in the frequency of ICAM-1 methylation status between GD or HT and healthy individuals were statistically significant (p = 0.04, 0.018 respectively) whereas there was no significant difference between GD and HT patients (p > 0.05). There was a correlation between decreased ICAM-1 methylation and exophthalmos (p = 0.01) and the high TSI level (p < 0.002) in GD patients. However, there was no correlation between ICAM-1 methylation and other clinicopathological features or other laboratory parameters in GD or HT. Furthermore, ICAM-1 mRNA expression showed significant up-regulation in ICAM-1 un-methylated samples compared to methylated samples in both GD and HT patients (p < 0.001 for each). Results provided the evidence of association of the hypo-methylation status of ICAM-1 gene promoter with GD and HT patients. In addition, DNA methylation may have a critical role in the ICAM-1 expression regulation of AITD patients.