Interleukin-1 (IL-1) is a cytokine involved in the maturation and proliferation of B cells and plays a significant role in the development of lytic bone lesions, a major clinical feature of multiple myeloma (MM) patients. Genes that regulate products involved in the immune system are highly polymorphic and contribute to inter-individual differences that can influence the genetic predisposition and progression of particular diseases and cancers. In this study, we investigated the correlation between the single nucleotide polymorphisms IL1A -889, IL1B -511, IL1B +3954, IL1RN Mspa1 +11100 and susceptibility to MM in 74 patients and 160 controls. We found that individuals possessing IL1A -889 CT polymorphism had a higher risk in developing MM. Moreover, genotypes IL1B -511 CC, IL1B +3954 CC, IL-1RN Mspa1 +11100 CC and the combination of IL1B +3954 CC with IL1B -511 CC or IL-1RN Mspa1 +11100 CC exerted a protective effect in individuals possessing them.