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Abstract Background The persistent the inflammatory condition in multiple sclerosis (MS) may due to the aberrant regulation of the elimination of the pathogenic autoreactive lymphocytes through apoptosis. Survivin, encoded by the BIRC5 gene, has been indicated to be involved in the regulation of apoptosis. This survey intended to investigate the genetic and microRNA mediated regulation of survivin in relapsing-remitting MS (RRMS) disease. Results It was observed that the C allele (OR = 1.38, 95% CI = 1.05–1.348, P = 0.022) and CC genotype (OR = 1.84, 95% CI = 1.06–3.19; P = 0.029) in the rs9904341 polymorphism increased the disease risk. Furthermore, miR-34a was significantly downregulated (Fold change = 0.41, P = 0.001) in the PBMCs from RRMS subjects. Survivin mRNA expression in PBMCs and serum survivin level were increased in RRMS patients in comparison to the controls. Downregulation of miR-34a was negatively correlated with increased survivin level. Conclusion Although the genetic polymorphism of BIRC5 gene was associated with the disease risk, miR-34a was suggested to be involved in the regulation of survivin in the RRMS patients.