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• Interleukin-2 (IL-2) gene polymorphisms have been studied in both solid and hematological malignancies. • In this study, it was aimed to examine the effects of IL-2RA rs2104286, IL-2 rs2069762 and rs2069763 polymorphisms on multiple myeloma susceptibility and survival. • IL-2 polymorphisms had no effect on disease susceptibility. • Patients with the TG genotype of IL-2 rs2069762 had a significantly shorter median progression-free survival (PFS) and overall survival compared to others. • Patients with the GG genotype of IL-2 rs2069763 had a significantly shorter median PFS compared to others. Interleukin-2 (IL-2) is a cytokine secreted from T helper type 1 cells and released after induction of T helper cells with major histocompatibility complexes or antigens presented by antigen presenting cells. IL-2 activity and gene polymorphisms have been studied in both solid and hematological malignancies. In the present study, it was aimed to examine the effects of IL-2RA rs2104286, IL-2 rs2069762 and rs2069763 polymorphisms on multiple myeloma (MM) susceptibility, progression-free survival (PFS) and overall survival (OS). A total of 300 patients diagnosed with MM in our clinic between January 2010 and January 2021, and 170 healthy individuals were included. In addition to the demographic data of the patients, MM subtypes, initial stages, prognostic index scores, laboratory results, treatment preferences, and survival data were recorded. The genotypes of the IL-2RA rs2104286, IL-2 rs2069762 and rs2069763 polymorphisms were statistically compared between patients and healthy controls to reveal their effects on MM susceptibility and survival. In the statistical analysis performed to examine the effect of IL-2RA rs2104286, IL-2 rs2069762 and rs2069763 polymorphisms on disease susceptibility, no significant difference was found between the patient and healthy control groups. Patients with the TG genotype of IL-2 rs2069762 had a significantly shorter median PFS and OS compared to others. Patients with the GG genotype of IL-2 rs2069763 had a significantly shorter median PFS compared to others. Having the TG genotype of IL-2 rs2069762 has been shown to be protective for short PFS and OS. Our study results will be guiding in terms of IL-2 based therapies, the future for MM and MM epigenetics. [ABSTRACT FROM AUTHOR]