Background: This study aimed to evaluate the role of Dickopff 1 (DKK1) serum levels as a marker for early detection of hepatocellular carcinoma (HCC) and to compare it with alphafetoprotein (AFP) after non-surgical intervention (microwave ablation, radiofrequency ablation) in HCC. Patients and methods: This prospective study was conducted in Al-Mahalla hepatology teaching hospital from June 2015 to June 2017. One hundred and twenty patients were included. They were classified into four groups: Group A: 40 patients with chronic liver disease; Group B: 40 patients with HCC which were divided into 2 main sub groups, group Ba which included HCC patients who were not eligible for ablative therapy and group Bb which included HCC patients who were eligible for ablative therapy; Group C: 20 healthy control subjects matched for age and sex; Group D: 20 HCC patients with negative AFP, DKK1 was done for them. Results: There was a highly significant difference (p < 0.001) between groups regarding serum level of Dickpoff 1 with mean of 1 ng/mL in group A (cirrhotic), 2.38 ng/mL in group B (HCC), and 1.83 ng/mL in group D (AFP negative HCC) in comparison to control group C with mean of 0.54 ng/mL. There was a highly statistically significant difference (p value less =0.01) in the studied groups regarding serum Dickpoff 1 before and after intervention with a mean of 2.38 ng/mL before intervention and mean of 1.37 ng/mL after 1 month of intervention. Conclusion: Serum Dkk-1 has higher sensitivity, specificity, and accuracy in early diagnosis of HCC than AFP.