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There is a relationship between the life cycle of the hepatitis C virus (HCV) and the synthesis and hemostasis of lipids as well as lipid metabolism and interferon (IFN) regulatory system. This study aimed to examine the effect of fluvastatin and IFN-γ in the expression of mediators involved in lipid metabolism and HCV proliferation in patients with rs12979860 CC polymorphism. Thirteen patients with HCV and five controls with rs1297986CC polymorphism were included in this study. Peripheral blood mononuclear cells (PBMCs) of patients and controls were treated by fluvastatin, IFN-γ or fluvastatin+IFN-γ. Assessment of IL-28B polymorphism, RNA extraction, and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was performed. The mRNA expression of sterol regulatory element-binding protein 1 c (SREBP1c), ATP-binding cassette transporter A1 (ABCA1), diacylglycerol acyltransferase 1 (DGAT1), and HCV core as well as measurement of ABCA1 protein level were evaluated before and after treatment. The results indicated that IFN-γ +fluvastatinacted as an inhibitor in mRNA expression of SREBP1c; while acting as an inducer in the expression of ABCA-1. The results of ABCA1 assay showed a significant increase of this protein after treatment with fluvastatin and IFN-γ compared with untreated cells (p=0.02). Moreover, the mRNA expression of HCV core was suppressed in all experimental groups treated with fluvastatin, IFN-γ or their combination which was more significant after treatment with fluvastatin+IFN-γ (p<0.001). The results of this study demonstrated the significant effect of treatment with fluvastatin+IFN-γ in PBMCs of HCV patients with rs12979860 CC polymorphism. According to the drug resistance of viruses and prevention of virus-induced steatosis in patients with HCV, using regulatory agents of lipid mediators in parallel with current medications could be considered as an effective therapeutic strategy. [ABSTRACT FROM AUTHOR]