Background: Hepatocellular carcinoma (HCC) is the major hepatic complication that may arise after many years of hepatitis C virus (HCV) infection. In Egypt, HCV represents the major health problem, also human cytomegalovirus (HCMV) is known as one of the highest un-resolved latent infections among general population. HCMV viremia in the co-infection with HCV may cause life threatening in HCC patients. Our study aimed to detect HCMV viremia in HCV–patients experienced HCC, and to investigate its role in disease worsening. Methods: In HCC patients, HCV-RNA viral load was determined by real- time polymerase chain reaction. In HCV-HCC patients, HCMV-DNA was detected by amplification of gB gene region using nested- polymerase chain reaction. Results: HCMV-DNA was detected in 4/73 in control subjects with prevalence rate of 5.4%, whereas HCMV–DNA was recorded in 24/75 HCV-HCC patients with prevalence rate of 32 %. Data on the level of  alpha feto protein (AFP) was available for 59 out of 75 HCV-HCC patients, this enabled us to differentiate between low risk HCC group of  40/59 patients with AFP < 500 ng/ml, from them HCMV- DNA  was detected in 14/40 patients with prevalence rate  35%, and high risk HCC group of 19/59 patients with AFP > 500 ng /ml, from them HCMV-DNA was reported in 9/19 patients with prevalence rate 47.37%. High significant prevalence rate of HCMV-DNA (P < 0.001) among control and HCC subjects was reported. Significant change in HCMV – DNA prevalence between low and high risk HCC groups could not be achieved but tendency of higher prevalence rate in HCMV- DNA was observed towards HCC high risk group of patients. Conclusion: we illustrated information about HCMV/ HCV co-infection in HCC patients, which referred to the association of HCMV viremia with HCV-HCC patients, as well as the tendency of elevation in HCMV viremia from low to high risk HCC patients depending on AFP threshold of 500 ng/ml.