In the present study, we investigated the B-cell translocation gene 1 (BTG1) as a candidate for multiple sclerosis (MS) susceptibility. BTG1 is a member of a family of genes involved in the apoptotic process. We genotyped two SNPs of the BTG1 gene (rs731652 and rs12694) in 550 MS patients and 548 controls. For SNP rs731652, significant associations with relapse-onset MS were found at the allele and genotype levels when compared with controls. We identified a risk haplotype associated with relapse-onset MS. These findings support the hypothesis that BTG1 polymorphisms may influence genetic predisposition for MS, especially in relapse-onset MS patients.