Endophytes are microorganisms that grow in the tissues of higher plants without causing any harm on the plants. They have been proven to be a rich source of bioactive natural products particularly in antioxidant properties. A previous study showed that endophytic Aspergillus sp. strain (HAB10R12) produces a series of secondary metabolite compounds with cytotoxic properties. In this study, levels of phenolic compounds (one of antioxidant properties) from the endophytic pyrone rich extract was measured by total phenolic content (TPC) assay. Subsequently, anti-proliferative effect of the extract was tested against human breast adenocarcinoma (MCF-7), colonic carcinoma (HCT116), adenocarcinoma human alveolar basal epithelial (A549) and human hepatocellular cancer (HepG2) cell lines using 3-(4, 5-dimethylthiazole2yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The endophytes exhibited the most potent effect against HepG2 (IC 50 = 0.024 μg/mL) followed by MCF-7 (IC 50 = 0.347 μg/mL), HCT 116 (IC 50 = 0.368 μg/mL) and A549 (IC 50 = 0.850 μg/mL) at 0.0379 ± 0.001 mg / 100 mg GAE of TPC. The findings reveal that the endophytic pyrones have potent anti-proliferative effects in-vitro.