Hepatitis C virus(HCV) is a hepato- and lymphotropicagent that is able to induce several autoimmune rheumatic disorders: vasculitis, sicca syndrome, arthralgias/arthritis and fibromyalgia. The severity of clinical manifestations is variable and sometimes lifethreatening. HCV infection can mimic many primitive rheumatic diseases, therefore, it is mandatory to distinguish HCV-related manifestations from primitive ones because the prognosis and therapeutic strategies can be fairly dissimilar. The new direct-acting antivirals drugs can help to avoid the well-known risks of worsening or new onset of autoimmune diseases during the traditional interferon-based therapies. The severity of clinical manifestations is variable and sometimes lifethreatening. HCV infection can mimic many primitives rheumatic diseases, therefore, it is mandatory to distinguish HCV-related manifestations from primitive ones because the prognosis and therapeutic strategies can be fairly dissimilar. The new direct-acting antivirals drugs can help to avoid the well-known risks of worsening or new onset of autoimmune diseases during the traditional interferon-based therapies.