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Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, with increasing global incidence. Morbidity and mortality associated with HCC remains high, and HCC is the leading cause of cancer death worldwide. Early detection and treatment of HCC can increase five-year survival by over 60%. Detection of HCC remains challenging, however, as HCC arises from a variety of environmental, genetic, and viral etiologies, and it demonstrates a complex pathophysiology and displays a heterogeneous morphology. Current diagnostic methods rely on abdominal ultrasound with or without concurrent AFP biomarker testing for high-risk individuals. This review provides an overview of HCC diagnostic modalities and highlights the promising nature of translational developments in biomarkers, next generation sequencing (NGS), artificial intelligence, molecular imaging, and liquid biopsy for earlier and more accurate diagnosis of HCC. Furthermore, we identify areas for improvement that must be addressed before the widespread usage and implementation of these methods.