_____________________________________________________________________________________________________ *Corresponding author: E-mail: thesismses@gmail.com; Journal of Advances in Medicine and Medical Research 34(20): 70-77, 2022; Article no.JAMMR.89013 ISSN: 2456-8899 (Past name: British Journal of Medicine and Medical Research, Past ISSN: 2231-0614, NLM ID: 101570965) Diagnostic Study of Serum Dickkopf 1 Level and Alpha Fetoprotein L3 as Tumor Biomarkers in Hepatocellular Carcinoma Amira Mohamed El Sharkawy a* , Mohammed Hosny Fouda a , Dina Hazem Ziada b and Gihan Farouk Attia a a Clinical Pathology Department, Faculty of Medicine, Tanta University, Tanta, Egypt. b Tropical Medicine and Infectious Diseases Department, Faculty of Medicine, Tanta University, Tanta, Egypt. Authors’ contributions This work was carried out in collaboration among all authors. All authors read and approved the final manuscript. Article Information DOI: 10.9734/JAMMR/2022/v34i2031469 Open Peer Review History: This journal follows the Advanced Open Peer Review policy. Identity of the Reviewers, Editor(s) and additional Reviewers, peer review comments, different versions of the manuscript, comments of the editors, etc are available here: https://www.sdiarticle5.com/review-history/89013 Received 24 April 2022 Accepted 01 July 2022 Published 01 July 2022 ABSTRACT Background: Alpha Fetoprotein (AFP) is now the most frequently applied tumour biomarker for the early diagnosis and clinical follow-up of HCC patients. Dickkopf 1 (DKK 1) is a protein that has a role in embryonic head morphogenesis. Several investigations revealed that DKK 1 regulates a variety of pathological and physiological processes. The aim of this work was to evaluate the diagnostic role of serum DKK 1 level and AFP- L3 as tumor markers in hepatocellular carcinoma. Methods: This observational research enrolled 60 participants aged above 18 years, group 1 include 10 healthy control participants, group 2 involved 25 cirrhotic cases and group 3 involved 25 cases diagnosed with HCC. All cases underwent taking of full history, clinical assessment, radiology, laboratory examination and specific investigations such as the tested two markers AFP- L3 and DKK1. Results: AFP-L3 had 84% sensitivity and 67.7% specificity, while DKK1 had sensitivity and specificity of 76% and 80% respectively to differentiate between cirrhotic and HCC cases, using a cut-off value of 8.62 ng/ml. two markers combination had specificity and sensitivity of 92%, 72% respectively and increase the accuracy for detection of HCC up to 82%. Conclusions: Both AFP-L3 and DKK1 could act as surrogate biomarkers for HCC and combination of two markers should be kept in mind to reach the optimum accuracy. Original Research Article