OBJECTIVE To investigate the prevalence and clinical significance of hepatitis C virus (HCV) infection in patients with systemic lupus erythematosus (SLE). METHODS Serodiagnosis was conducted in 134 SLE patients and 200 volunteer blood donors to examine the antibodies of HCV with enzyme-linked immunosorbent assay-3 (ELISA-3). Recombinant immunoblot assay-3 (RIBA-3) and PCR were performed to verify the results. RESULTS HCV infection was present in 15 patients with SLE (11.8%) and in 2 volunteer donors (1%, P<0.001). Compared with the SLE patients without HCV infection, the patients with HCV infection had a lower rate of cutaneous SLE features and dsDNA positivity (P=0.01 and P<0.001), but with higher incidences of hepatic damage (P<0.001) and low levels of C4 and CH50 (P=0.01 and P=0.03) as well as cryoglobulins levels (P=0.03). CONCLUSIONS The prevalence of HCV infection is higher in SLE patients than in non-SLE subjects, and SLE patients with positive HCV show a lower rate to present cutaneous SLE features and positive dsDNA antibody, but who have higher possibilities of hepatic damage, hypocomplementemia and cryglobulinemia.