Hepatitis B virus (HBV) and hepatitis C virus (HCV) chronically cause hepatitis, liver cirrhosis, and hepatocellular carcinoma, and biomarkers related to liver damage are elevated in HBV and HCV patients. However, comparisons of biomarkers between HBV and HCV patients have not previously been reported. The aim of this study was to investigate differences in hematological biomarker in the sera of HBV and HCV patients and to find a key biomarker to differentiate between HBV and HCV infections. HBV (n=115) and HCV (n=128) samples (serum and whole blood) were collected and tested using a biochemical analysis system. The obtained data were analyzed with SPSS 18.0 statistical software. The mean age of the HCV group (60.3±14.1) was much higher than that of the HBV group (51.1±12.4). Male and female rates were 71.3% and 28.7% in the HBV group and 53.9% and 46.1% in the HCV group, respectively (p = 0.005). AST, ALT, and TG values were higher in the HCV group than in the HBV group. Although γ-GTP and LDL levels were higher in the HBV group than in the HCV group, apoB and apoE levels were much higher in HCV group than in HBV group (p < 0.001). There were no significant differences in the other hematological biomarkers between the HBV and HCV groups. In conclusion, HBV rates were higher in male patients, and HCV rates were higher in older patients. In particular, apoE and apoB were more highly expressed in HCV patients, and they might be key markers to differentiate HCV infection.