ABSTRACT Background: Abnormal autocrine fibroblast growth factor 19 (FGF19) productions have been observed in several types of cancers, including hepatocellular carcinoma (HCC), which is considered 3rd cause of cancer deaths worldwide with gradually increased incidence. Objective: To investigate the role of FGF 19 in prediction, diagnosis and follow up of HCC together with alpha feto protein (αFP). Patients and methods: This study was carried in Internal Medicine Department and Clinical Pathology Department, Faculty of Medicine Zagazig University Egypt in the period from October 2017 to October 2020. The study included 150 patients (111 males and 39 females) classified into 3 groups: 50 healthy volunteers as a control, 50 patients with liver cirrhosis documented by examination and investigation and 50 Patients with HCC with variable sizes. All participants in the study were subjected for the following after written consent and approval by their search ethics committee of Zagazig University. Result: The median of FGF19 level between control, liver cirrhosis and HCC was 4, 6 and 10 87 pg/ml respectively with higher sensitivity for detection of small HCC with high significance of α Fp between HCC > cirrhosis > control. Conclusion: FGF19 can be used successfully as a novel biomarker for HCC diagnosis and follow up after treatment together with already existing biomarker α FP.