Peripheral blood mononuclear cells (PBMC) constitute the main extrahepatic reservoir of hepatitis C virus (HCV). Lipid metabolism of host seems to play important role in HCV infection. The relationship between HCV presence in PBMC and the expression of mevalonate pathway has not been elucidated. The aim of this study was to investigate the association between mevalonate pathway and HCV RNA presence in PBMC after anti-HCV treatment. 67 serum and corresponding PBMC samples were collected from patients at the end of interferon alpha and ribavirin treatment. Serum total cholesterol, HDL-C and LDL-C fractions, triglycerides, as well as intracellular cholesterol and expression level of HMG-CoA reductase, geranylgeranyl pyrophosphate synthase in PBMC were measured and matched for the HCV RNA presence or absence in sera/PBMC. HCV RNA elimination from sera and PBMC was associated with higher serum cholesterol (118.5mg/dL) and LDL-C (66.42mg/dL) levels, compared to the group, where HCV RNA was detected only in PBMC (100.94 and 53.22mg/dL) or the group, where HCV RNA was found in both sera and PBMC (86.79 and 43.79mg/dL) after treatment. Increased expression of geranylgeranyl pyrophosphate synthase was found in the majority of PBMC samples that harbored HCV RNA after elimination of HCV RNA from sera. The expression of mevalonate pathway after antiviral treatment seems to be modulated depending on HCV RNA status in peripheral blood mononuclear cells.