IL-32 is a proinflammatory cytokine that establishes a positive feedback loop with other cytokines associated with autoimmune diseases. Limited studies are available about the role of IL-32 in psoriatic arthritis. In this study, we investigated the mechanisms by which IL-32 contributes to disease pathogenesis in psoriatic arthritis. First, we measured IL-32 levels in the synovial fluid of patients with psoriatic arthritis, rheumatoid arthritis, and osteoarthritis, and found that IL-32 levels are significantly greater in psoriatic arthritis and rheumatoid arthritis compared to the non-inflammatory condition osteoarthritis. Next, we cultured synovial fibroblasts from patients with psoriatic arthritis with IL-32 (α and γ subtypes), other proinflammatory cytokines, or media alone and measured cell proliferation with MTT/CFSE assays. We found that synovial fibroblasts stimulated with IL-32 had significantly more growth than synovial fibroblasts stimulated with media. We also measured the levels of other cytokines/chemokines/endopeptidases in the supernatant of synovial fibroblasts stimulated with IL-32 and media, and found that the concentrations of IL-6, IL-8, MMP3, and RANK-L were significantly greater in the supernatant of synovial fibroblasts stimulated with IL-32 compared to media. Results of this study suggest that IL-32 contributes to psoriatic arthritis pathogenesis by inducing synovial fibroblast proliferation causing pannus formation, upregulating other pro-inflammatory cytokines, and increasing RANK-L expression/osteoclast activation leading to erosive disease. Given its role in disease pathogenesis, it is possible that IL-32 could be a novel therapeutic target for the treatment of psoriatic arthritis.