Background Hepatocellular Carcinoma (HCC) stands as the third most fatal malignancy worldwide, accounting for over 830,000 fatalities annually. This pressing concern has spurred extensive research into potential early diagnostic biomarkers, with a particular focus on the role of vascular endothelial growth factor (VEGF) in recognizing angiogenesis within HCC. VEGF offers an intricate insight into the angiogenic processes, among its multifaceted advantages. Methods We systematically curated articles from PubMed and Epistemonikos, concentrating on the determination of VEGF’s diagnostic cutoff value, sensitivity, and specificity for HCC. Employing the PRISMA 2020 flowchart, we meticulously delineated the process of article selection. Results In total, our review encompasses nine studies, encompassing 576 HCC patients, subject to qualitative analysis. The collective findings indicate that the specificity of VEGF outweighs its sensitivity, indicating its aptitude in distinguishing HCC from both a healthy population and other high-risk conditions, most notably in comparison with these high-risk conditions. Specificity holds pivotal significance as a preferred parameter for a screening test, endorsing the prospective utility of VEGF in HCC screening. Conclusions For individuals, especially those within the normal alpha-fetoprotein range, VEGF may serve as a viable alternative for HCC screening, facilitating the differentiation of this condition from other high-risk conditions.