Background: The multifunctional cytokine interleukin-6 (IL-6) is involved in inflammatory processes in the central nervous system. It is well documented that amount of IL-6 is increased in serum, cerebrospinal fluid and central nervous system lesions of patients with multiple sclerosis. A single nucleotide polymorphism at position -174 in the IL-6 gene promotor appears to influence IL-6 expression. Recently, several researchers have focused on HLA-DRB alleles, specifically HLA-DRB1*1501, as a potential risk allele in the pathogenesis of multiple sclerosis. Objective: To investigate the possible influence of IL-6/-174 polymorphisms on susceptibility to multiple sclerosis and its integration with HLA-DRB1*1501. Genomic DNA was extracted from whole blood of 345 patients with multiple sclerosis and 426 control subjects. Method: The SSP-PCR method was used to determine genotypes and Fisher's exact test was applied to determine differences between groups. HLA-DRB1*1501 was observed more frequently among multiple sclerosis patients compared with healthy subjects (45% and 34%, respectively; OR = 1.6, 95% CI = 1.2-2.2, p = 0.0018). At the IL-6/-174 position, the G allele had higher frequency among multiple sclerosis patients compared with controls (77% and 70%, respectively; OR = 1.4, 95% CI = 1.1-1.8, p = 0.0038). This difference was more significant among HLA-DRB1*1501-positive patients and controls (81% and 67%, respectively; OR = 1.9, 95% CI = 1.5-2.5, p < 0.0001). Results: Our results have shown that the G allele at the IL-6/-174 promoter polymorphism may be associated with development of multiple sclerosis in this population, and may be strengthened by HLA-DRB1*1501. Conclusions: We suggest more studies to confirm these results in other populations.