The lncRNA Growth arrest-specific 5 (GAS5) has crucial roles in the apoptosis, suppression of cell growth and regulation of response to glucocorticoids. Previous studies have demonstrated its role in the pathogenesis of some immune-related disorders such as systemic lupus erythematosus and multiple sclerosis (MS). In the current study, we genotyped two possibly functional GAS5 polymorphisms (rs2067079 and rs6790) in 810 individuals including 410 MS patients and 400 age and sex-matched healthy subjects. There was a significant over-representation of the rs2067079 T allele in MS patients compared with healthy individuals (OR (95% CI) = 1.38 (1.12-1.71), adjusted P value = 0.008). This SNP was associated with MS risk in co-dominant and recessive models (OR (95% CI) = 2.70 (1.54-4.76), adjusted P value = 0.003; OR (95% CI) = 2.58 (1.5-4.42), adjusted P value = 7.9E-4 respectively). The rs6790 was not associated with MS risk in any inheritance models. The T G haplotype (rs2067079 and rs6790 respectively) was significantly more prevalent among cases compared with controls (OR (95% CI) = 1.48 (1.16-1.89), adjusted P value = 0.005). Our results further highlight the role of GAS5 in the pathogenesis of MS.