This study aimed to evaluate the expression of miR-203 and serum endocan in Hepatocellular carcinoma (HCC) patients suffered from hepatitis C virus (HCV) or hepatitis B virus (HBV) to investigate their diagnostic value. This study was conducted on 70 patients divided into 29 HCC [20 on top of HCV and 9 on top of HBV], 41 non-HCC chronic liver disease [20 positive HCV and 21 positive HBV] patients. Ten healthy volunteers were recruited as controls. The expression of miR-203 was detected using quantitative real time (qRT-PCR). Serum endocan was assessed by Enzyme linked immunosorbent assay (ELISA). The results indicated that there was a significant reduction in miR-203 expression level in HCC-related HCV group compared to HCV (p<0.001) and control group (p<0.001) and in HCV group compared to controls (p<0.001). On the other hand, there was a significant increase (p<0.001) in miR-203 HCC-related HBV group compared to HCC-related HCV group, with a significant elevation (p<0.01) in HBV versus HCV group. At a cutoff value of 0.3276, miR-203 showed 100% sensitivity and 90% specificity [AUC=0.989] in HCC-related HCV group. Serum endocan was significantly elevated (p<0.05] in HCC patients versus controls. A significant increase (p<0.05] was found in HCC-related HCV compared to HCV group, with a significant diminution (p<0.001) in HBV group versus controls. HCV patients showed a significant increase (p<0.05) in endocan level compared to HBV ones. In conclusion: miR-203 and serum endocan could be used as diagnostic markers for HCC related different viral infection in the Egyptian patients. Further research is required to confirm our findings.