Aim: Protective effects of aqueous extract of Amaranthus hybridus against afl atoxin B 1 (AFB 1 ) and/or fumonisin B 1 (FB 1 ) on the H4IIE-luc cell line were determined by use of the methyl thiazol tetrazolium viability assay and disruption of DNA integrity. Methods: H4IIE-luc cells were incubated with different concentrations of AFB 1 and/or FB 1 for 24 and 48 h with or without aqueous extract of A. hybridus. Results: AFB 1 decreased the viability of cells after 24 and 48 h of exposure. EC 50 values for AFB 1 were 10.5 and 1.8 μmol/L for the two periods, respectively. When the 48 h exposure to mycotoxin repeated with a pre-treatment of 20 and 40 μg/mL extract of A. hybridus, the EC 50 changed to 3.88 and 7.67 μmol/L, respectively. H4IIE-luc cells exposed to FB 1 for 24 h responded more than those incubated for 48 h. Cells treated with a combination of AFB 1 and FB 1 were less viable with a signifi cant decrease in the greater concentration. The mixture of AFB 1 and FB 1 resulted in a signifi cant threat to H4IIE-luc as indicated by the absence or appearance of new bands in random amplifi ed polymorphic DNA analysis, which demonstrated damage to DNA. The protective effects were probably due to greater content of total phenolics, carotenoids, β-carotene, folic-, linolenic-, linoleic and palmitic acids, as well as calcium, magnesium, iron, zinc, and selenium observed in the extract. Conclusion: Exposure to 40 μg/mL of extract of A. hybridus protected cells from damage to DNA by stabilizing DNA. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.