Background: Hepatocellular carcinoma (HCC) is the fifth most common malignancy. Midkine (MK) is a cytokine or a growth factor belongs to the carbohydrate-binding proteins. MK is over expressed in hepatocellular carcinoma. Furthermore, patients with high MK expression in the tumor frequently have a worse prognosis than those with low MK expression. Objectives: The aim of the work was to evaluate serum midkine as a marker for Hepatocellular carcinoma in cirrhotic patients. Patients and Methods: This study was conducted on 90 subjects who were divided into three groups: group I included 40 patients with liver cirrhosis and hepatocellular carcinoma, group II included 40 patients with HCV related liver cirrhosis without HCC and group III with 10 healthy subjects as controls. Plasma level of midkine was measured for all subjects. Results: Serum levels of midkine were highest in patients of group I with HCC compared to those with liver cirrhosis and the control groups (p value< 0.001). Also midkine values increased with tumor number and overall size. According to the ROC curve, the best cutoff value for midkine differentiating HCC from liver cirrhosis cases was 8500pg/mL, above which the sensitivity to discriminate HCC = 100% and below which the specificity to discriminate liver cirrhosis = 87.5% with 94.5% accuracy. Conclusion: Serum midkine level was significantly elevated in HCC patients, so it can be used as a diagnostic marker for HCC. Also, it was directly correlated to the tumor number and overall size so it has a good prognostic value.