The aim of this study was to evaluate serum levels of interleukin-1β (IL-1β), chemokine (C-X-C motif) ligand 10 (CXCL10), and interferon-gamma (IFN-γ) in a series of patients with "mixed cryoglobulinemia and hepatitis C virus chronic infection" (MC + HCV) in the presence or absence of autoimmune thyroiditis (AT) and to relate them to the clinical phenotype of these patients. Serum IL-1β, IFN-γ, and CXCL10 were assayed in 30 patients with MC + HCV without AT, in 30 patients with MC + HCV and AT, and in 30 sex- and age-matched controls. Cryoglobulinemic patients showed significantly higher mean IL-1β and CXCL10 levels than controls (P < 0.01). Moreover, CXCL10 was significantly increased in patients with AT patients with respect to those without AT (P < 0.01). Serum IFN-γ levels were not significantly higher in MC + HCV patients than in controls. In conclusion, our study demonstrates significantly high serum levels of IL-1β in patients with MC + HCV with and without AT compared with healthy controls. Further, significantly high serum levels of CXCL10 in patients with MC + HCV compared with healthy controls were confirmed, overall in the presence of AT. Moreover, a pathophysiological association between high circulating levels of IL-1β and CXCL10 has been suggested. A possible therapeutic role of the anti-IL-1 receptor antagonist (Anakirna) in MC remains to be evaluated.