The aim of this study was to assess the efficacy of non-invasive Midkineexpression level as diagnostic biomarkers of Hepatocellular Carcinoma and its relationship with diagnostic parameters. Thirty six subjects were enrolled in the present study, they were divided into three groups: Group (A) included 10 apparently healthy subjects as acontrol group; Group (B) included 14 HCC patients ; Group (C) included 12  HCV patients ; The studied groups under study were age and sex matched. Routine and specific (MDK) laboratory investigations were performed in all included subjects. The median age of the patients was 51 years (rang 44-58 years); where males represented the majority of the groups (69.4%). MDK expression level was detected by quantitative polymerase chain reaction (qRT-PCR). None of the patients were pretreated with local therapies. The MDK level was significantly higher in patient HCC than in the HCV and control groups (p=0.028), whereas MDK level was also higher in HCV patient than healthy patient. Further the correlation between the level of MDK and all laboratory parameters was tested. In this study there is a good positive correlation between MDK levels and SGPT (AST), and SGOT (ALT). The sensitivity and specificity of AFP were 75.7%    and 86.4% respectively, while those of MDK were 64.3% and 77.3%, respectively, in early-stage HCC patients but when combinations between two markers lead to higher sensitivity 100% to predict HCC patient.