Hepatocellular carcinoma (HCC) is a prevalent malignancy and there is a lack of effective biomarkers for HCC diagnosis. Living organisms are complex, and different omics molecules interact with each other to implement various biological functions. Genomics and metabolomics, which are the top and bottom of systems biology, play an important role in HCC clinical management. Fatty acid metabolism is associated with malignancy, prognosis, and immune phenotype in cancer, which is a potential hallmark in malignant tumors. In this study, the genes and metabolites related to fatty acid metabolism were thoroughly investigated by a dynamic network construction algorithm named EWS-DDA for the early diagnosis and prognosis of HCC. Three gene ratios and eight metabolite ratios were identified by EWS-DDA as potential biomarkers for HCC clinical management. Further analysis using biological analysis, statistical analysis and document validation in the discovery and validation sets suggested that the selected potential biomarkers had great clinical prognostic value and helped to achieve effective early diagnosis of HCC. Experimental results suggested that in-depth evaluation of fatty acid metabolism from different omics viewpoints can facilitate the further understanding of pathological alterations associated with HCC characteristics, improving the performance of early diagnosis and clinical prognosis.