<i>In vivo</i>, <i>MARCKS</i> silencing significantly suppresses tumor growth and vascularization.<h4>Discussion</h4>Our findings reveal a critical role for venous endothelial cells in HCC angiogenesis and identify <i>MARCKS</i> as a potential therapeutic target, providing molecular insights for precision oncology in HCC. The gene discussed is MARCKS; the disease is hepatocellular carcinoma.