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Hidradenitis Suppurativa (HS) is a chronic, inflammatory, and relapsing skin disease. Pathogenesis of the disease is not well understood, but many studies revealed the potential role of cytokines and interleukins. IL-36 expression was increased in tissue samples of HS patients with conflicting result regarding serum levels. To investigate serum IL-36 levels in HS patients and evaluate their relation to disease characteristics, 44 patients diagnosed with HS and 44 age and sex-matched healthy controls were included in the study. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum IL-36 concentrations. Serum levels of IL-36α, IL-36β, and IL-36γ were significantly elevated in HS patients compared to healthy controls (all three p < 0.001). IL-36α, IL-36β, and IL-36γ levels were significantly higher in current smokers compared to non-smokers and positively correlated with number of packs/year (p = 0.002, r = 0.402; p = 0.042, r = 0.242 and p = 0.001, r = 0.391, respectively). IL-36α, IL-36β, and IL-36γ levels were also elevated in obese patients and patients with metabolic syndrome (p = 0.007, < 0.001, 0.038, 0.004, 0.006, and 0.048, respectively). After stratified and restricted analyses for smoking, obesity, and metabolic syndrome IL-36α, IL-36β, and IL-36γ increased the risk of HS 11.0, 1.79, and 4.5 time, respectively (95% CI 1.7–71.28, p < 0.001; 95% CI 1.04–3.06, p = 0.005 and, 95% CI 1.007–20.106, p = 0.040, respectively). Elevated serum IL-36 levels may contribute to pathogenesis of HS and may be a candidate for future biological treatment of the disease. [ABSTRACT FROM AUTHOR]