Background and study aim: Hepatocellular carcinoma (HCC) accounts for 70 - 80% of all liver cancers and the 5-year survival is only 3 - 5%. This bad prognosis is due to the lack of an effective method for early diagnosis. So, only 30 - 40% of patients with HCC are suitable for curative treatments at the time of diagnosis. Thus, there is a great need for tools to diagnose HCC early especially in cirrhotic patients. The aim of this work is to assess the validity of serum DKK1 as a diagnostic marker for HCC and to assess prognostic value of serum DKK1 in predicting treatment response, complication and survival in HCC patients. Patients and Methods: This study included Session [CurrentTestPartID] Patients divided into two groups. Group A: consisted of 30 patients with post hepatitic C and/or B liver cirrhosis. Group B: consisted of 30 patients with HCC on top of post hepatitic C and/or B liver cirrhosis. Group B patients underwent either radiofrequency ablation or ethanol injection. Clinical assessment, routine laboratory evaluation, CT studies and measurement of serum alpha-fetoprotein (AFP) and DKK1 were performed to all patients and repeated to group B patients 1 and 3 months after treatment. Results: The optimum cut off value of DKK1 for diagnosis of HCC was 4.3 ng/mL (AUC 0.89, sensitivity 66.7% and specificity 96.6%)  (P<0.001). While, the optimum cut off value for AFP was > 101 ng/mL with 90% sensitivity and 75.9% specificity (p<0.001). Testing of both DKK1 and AFP increased the diagnostic accuracy for HCC (AUC 0.901, sensitivity 93.3%, and specificity 75.9) (P<0.001). Serum DKK1 level significantly decreases after HCC treatment with either radio-frequency ablation or ethanol injection (P<0.001). Conclusion: Testing of both DKK1 and AFP significantly increased the diagnostic accuracy for HCC. Meanwhile, DKK1 can be used alone for HCC diagnosis even in HCC with inconclusive AFP. DKK1 has a promising prognostic value and can be used for follow up of HCC patients who underwent loco-regional treatment.