Background & Objectives: Hepatocellular carcinoma and its complications with the multiplicity is crucial worldwide health problem especially  in the presence of heterogeneous liver. We aimed to assess the value of fatty acid binding protein-1in the diagnosis of hepatocellular carcinoma in comparison to alpha-fetoprotein. Methodology: One hundred subjects were enrolled in this observational case-control study who attended the Hepatology, Gastroenterology and Infectious Diseases Department in Benha University Hospitals between January 2018 and January 2019 and divided into 80 patients (40 HCC &40 LC and 20 healthy subjects). Serum level of fatty acid binding protein-1 was determined by enzyme-linked immunosorbent assay. Results: Hepatocellular carcinoma patients were slightly older than healthy subjects as mean age in group І was (56.1±9 yrs) while in group III was (52.9±17.1 yrs). There was a marked increase in hepatocellular carcinoma in males with male to female ratio 4:1. There was a high prevalence of hepatocellular carcinoma in the rural population. Fatty acid binding protein-1 was higher in hepatocellular carcinoma compared to liver cirrhosis and the control group, ranged from (107-1224 ng/L, 48-981 ng/L and 34-460 ng/L) respectively. Analysis of ROC curve revealed that at a level 214 ng/L sensitivity, specificity, PPV, NPV and accuracy were 60%, 77.5%, 72.7%, 66% respectively with AUC 0.715 Conclusion: The use of fatty acid binding protein-1especially in multicentric hepatocellular carcinoma will be valuable because  the difficulty in most cases to prove  the multiplicity of hepatocellular carcinoma.