Sungkai (Peronema canescens Jack) is known to have various bioactive compounds as anticancer agents. This study aims to evaluate the anticancer potential of the active compound from the ethyl acetate fraction of sungkai leaves through an experimental and computational approach. The cytotoxic activity of the ethyl acetate fraction was carried out using the MTT assay method on A549 lung cancer cells. The computational study carried out using the molecular docking method and continued with pharmacokinetic analysis of the five main compounds in the ethyl acetate fraction of sungkai leaves. The MTT assay revealed that the ethyl acetate fraction exhibited moderate cytotoxic activity against A549 lung cancer cells, with an IC₅₀ value of 33.41 µg/mL. The LC-MS/MS analysis identified five main compounds in this fraction: isorhamnetin, physcion, pilosin, (3R)-sophorol, and takakin. Molecular docking simulations of these compounds with the EGFR protein (PDB ID: 5UG9) showed bond energies ranging from -7.7 to -8.9 kcal/mol. Physcion has a more negative bond energy value compared to the positive control (quercetin) and four other compounds. The compounds interacted with the protein through hydrogen bonds and van der Waals interactions, predominantly involving amino acid residues ALA A:743, VAL A:726, LEU A:718, LEU A:844, and GLN A:791. Pharmacokinetic analysis revealed that all the compounds met Lipinski's rule of five, indicating good oral absorption and membrane permeation. However, toxicity predictions showed that isorhamnetin, takakin, and pilosin had a high risk of gene mutations, whereas physcion had a moderate risk. Despite potential toxicity concerns, the compounds had drug scores greater than 0, suggesting their potential as drug candidates. Therefore, experimental and computational approaches can be an efficient early screening method to identify potential bioactive compounds as drugs. However, further analysis must be carried out regarding the risk of toxicity and a good dose of the drug.