Hepatitis C virus (HCV) which is one of the endemic viral infections in Egypt is not only hepatotropic, but also a lymphotropic virus and has many extrahepatic manifestations as mixed cryoglobulinemia and non-Hodgkin's lymphoma. We studied gene expression profile of 20 B-cell non-Hodgkin's lymphoma with HCV infection and 20 B-cell non-Hodgkin's lymphoma without HCV infection as a control group by c-DNA microarray. Out of the 15,500 studied genes, more than 1000 genes were differentially expressed; either upregulated or downregulated. We found that HCV may rescue B lymphocytes from apoptosis possibly through causing suppression of CASP1 and CASP4 and causing overexpression of the anti-apoptotic BCL2 gene. Also, HCV was associated with overexpression of the genes related to myeloid/lymphoid leukemia and B lymphoma as MLLT3, BAL, influences the overexpression of transcription regulator genes as TATA box binding protein (TBP) and may influence the overexpression of some immunoglobulin genes as immunoglobulin superfamily containing leucine gene in B cells resulting in overproduction of immunoglobulins in B-lymphocyte disorders. Moreover HCV was associated with reduced expression of MHC class II molecules in B lymphocytes, and therefore inhibition of antigen processing and presentation through downregulation of different MHC class II molecules genes. We conclude that the upregulated and the downregulated genes identified through the studied expression profiles of NHL with HCV infection may shed light on the mechanisms of HCV lymphomagenesis.