Purpose <p>The interplay between genetic susceptibility and environmental triggers is critical in autoimmune diseases such as Hashimoto’s thyroiditis (HT). The aryl hydrocarbon receptor (<i>AhR</i>) gene plays a key role in gene-environment interaction and in modulation of immune responses. Given that environmental changes shape the selection of genetic variants, we hypothesized that polymorphisms in <i>AhR</i> may contribute to HT susceptibility.</p> Patients and methods <p>Two <i>AhR</i> single nucleotide polymorphisms (SNPs), rs2066853 (exon 10) and rs10249788 (promoter region), were analyzed in 200 unrelated subjects (100 HT patients and 100 matched healthy controls, HC). Genotyping was performed using restriction fragment length polymorphism analysis and nucleotide sequencing. All genotype distributions were in Hardy–Weinberg equilibrium.</p> Results <p>The rs10249788 (C &gt; T) variant was detected in 20/100 HT patients and 7/100 HCs. Genotype frequencies differed significantly between groups (<i>P</i> &lt; 0.05), with the heterozygous C/T genotype showing an odds ratio &gt; 3 and a significant association with HT. Multivariate analysis demonstrated that rs10249788 was independently associated with family history of HT and thyroid function (<i>P</i> &lt; 0.05). TSH levels increased progressively from C/C to variant genotypes, suggesting an influence of the T allele on thyroid functional expression. The rs2066853 (G &gt; A) variant was rare and showed no disease-specific relevance.</p> Conclusions <p>The <i>AhR</i> polymorphism rs10249788 (C &gt; T) is associated with Hashimoto’s thyroiditis, emerging as a potential genetic contributor to disease susceptibility and clinical expression.</p>