Background: Multiple sclerosis (MS) seems to be a multifactorial disease in which the environment and genetics are involved. One of the factors associated with MS disease is the reduction in vitamin D levels and its specialized role in its pathogenicity. In Iran, Khuzestan province has a high relative incidence of the Multiple sclerosis (MS) after the provinces of Isfahan and Markazi, The polymorphism rs10735810 in the VDR gene with change in the initial codon is one of the factors associated with other known diseases, including osteoporosis and diabetes. Methods: In this study, the association of this variant in one hundred and fifty individuals with MS disease was compared with one hundred and fifty healthy individuals. PCR-sequencing was used to determine genotypes. Results: In the patient group, 16 cases had CC genotype, 59 had CT genotype and 75 had TT genotype, which did not show any significant difference in comparison with the control group (P>0.05). Also, there was no significant difference in the alleles distribution in the patient population compared to control (50% vs. 47.55% P=0.47). Additionally, no association was found between age and sex, and the ethnicity of patients (p> 0.05). Conclusion: The polymorphism rs10735810 in the VDR gene showed no association to the etiology of MS.