Objectives: To investigate the capability of Vernonia cinerea extracts to disrupt the intracellular oxidative-antioxidative status in colorectal cancer cells. Methods: All experiments were conducted on two colorectal cancer cell lines (SW620 and HT29) with aqueous and ethanol extracts of Vernonia cinerea (VC). The cytotoxicity of both extracts was evaluated using MTT assay. Cells were treated for 1, 4, and 7 days with different concentrations of aqueous and ethanol extracts ranging from 100-700 and 10-150 μg/ml respectively. The antioxidant capacity of cell lysates was determined by the 2, 2'-azino-bis-(3-ethylbenzothiazolin-6-sulfonic acid) diammonium salt (ABTS), 2, 2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) radical scavenging activities, and malondialdehyde (MDA) inhibitory effect. The possible action mechanism was also investigated through gene expression of antioxidant enzymes, i.e. superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. Results: Both aqueous and ethanol extracts showed dose/time-dependent manners in all assays. Ethanol extract had a higher potency for cytotoxicity with obviously lower IC 50 and a higher antioxidant capability in cytoplasmic content than aqueous extract, especially at 4-day treatment. Low MDA content and gene expression alteration of four enzymes involved in antioxidant status were found in cells treated with ethanol extract compared to aqueous extract. Conclusions: Ethanol VC extracts can cause cytotoxicity to human colorectal cancer cells, possibly be involved in oxidative stress, and/or interfere with oxidative-antioxidative balance by radical scavenging in vitro.