Background: Hepatocellular carcinoma (HCC), a primary liver cancer, continues to pose a significant challenge to the healthcare system because of its elevated incidence and fatality rates. This study aims to assess new biomarkers for early diagnosis and prognosis, comparing them to the established gold standard alpha-fetoprotein (AFP) and liver ultrasonography. Methods: A literature review was conducted in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guideline. A total of 670 papers were identified using internet databases. After applying the exclusion criteria, eight studies were included in this literature review. Results: It was identified that certain analyzed biomarkers, or the combinations thereof, exhibited superior sensitivity compared to the existing gold standard. The circulating cell-free DNA (cfDNA) and microRNAs (miRNAs), proved to have encouraging outcomes, particularly for the early identification of HCC. Additional indicators, such as circulating tumor cells (CTCs) and the alkaline phosphatase plus gamma-glutamyl transpeptidase to lymphocyte ratio (AGLR), may forecast disease progression, particularly regarding vascular invasion. Conclusions: These biomarkers may assist clinicians in making better therapeutical choices in order to provide personalized treatment and optimal follow-up for HCC patients.