Many environmental and genetic factors have been implicated in the development of multiple sclerosis. However, the aetiology has not been clarified yet. Therefore, using a meta-analytic approach, we tried to probe the potential association between various cytokine gene polymorphisms and the occurrence of multiple sclerosis. A comprehensive literature search yielded 45 eligible studies, which involved 7379 cases and 8131 controls. Totally, the effect of eight polymorphisms, i.e. IL-1A C[-889]T, IL-1B C[-511]T, IL-1B CT, IL-4 CT, IL-10 C[-819]T, IL-10 G[-1082]A, tumour necrosis factor-a (TNFA) G[-308]A and TNFA G[-238]A, was evaluated in a random-effects meta-analysis. There was no evidence of statistically significant association between the aforementioned polymorphisms and multiple sclerosis. Publication bias and heterogeneity were absent in most analyses. Within its limitations, the current literature-based meta-analysis does not indicate that specific polymorphic variations of genes encoding pro-inflammatory and anti-inflammatory cytokines affect susceptibility to multiple sclerosis.