Hepatocellular carcinoma (HCC), the most prominent type of primary liver cancer, often diagnosed late, leading to poor prognosis and limited treatment options. This study investigated the anti-carcinogenic effect of Quinazoline-2,4(1H,3H)-dione (Qd), a quinazoline derivative of natural origin and identified Qd as an effective compound against HCC via STAT3 and FOXO3a signaling. STAT3 and FOXO3a are two well-known molecular drivers of HCC. In silico findings revealed Qd as the potent candidate due to its highly stable interaction with STAT3 and FOXO3a. To validate its anticancer activity, in vitro experiments were conducted on the HepG2 cell line. Qd exerts cytotoxic effect in HepG2 cells with an IC