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The cytotoxicity effects of Nigella sativa (Ns) and Zingiber zerumbet (Zz) extracts on acute Human myeloid leukemia cell line (HL60) are reported. The HL60 cell line was purchased from the American Tissue Culture Company (ATCC) was treated with petroleum ether (PE) and aqueous (AQ) extracts of Ns and Zz extracts of ethanol (ET) and Hexane (HEX). In an attempt to explain cytotoxicity effects of Ns and Zz extracts by 3-[4,5-dimethylthizol-2-yl]-2,5- diphenyltetrazolium bromide (MTT) assay, we examined the effects of Doxorubin (Dox) on their sensitivity as anticancer drugs which was assigns as a positive control in this experiment. Different plant species has different component as bioactive compound. The different activity is present by the different compound. The cytotoxicity effects of plant species are differed based on the presence of their bioactive compound. Therefore, this study was carried out to compare the cytotoxicity effects of Nigella sativa (Ns) and Zingiber zerumbet (Zz) extracts on HL60 cell lines since both of these plants are from different species. Furthermore, this study was also to compare the cytotoxicity effect of plant extract and its compound which are Ns extract and thymoquinone, Zz extract and zerumbone. In this study, Hexane extract of Zz significantly dropped off the percentage of cell viability of HL60 cell by giving the lowest IC50 value which is 63.72ug/ml (p<0.05). Hexane extracts is more effective solvent compared to ethanol that gave IC50 value of 345.3ug/ml. Ns extract is less effective on HL60 cell lines that gives the highest IC50 value which are 654ug/ml for PE and greater than 1000ug/ml for AQ. It is concluded that the cytotoxicity effects of Zz is more proficient as compared to Ns in this cell. HEX extract is more appropriate solvent for the Zz extraction that gave the lowest IC50 as compared to ET. In addition, PE extract shows the characteristic of more appropriate solvent for Ns extraction compared to AQ solvent since gives the lowest IC50 value. On the other hand, both of plant species showed apoptosis as mode of cell death.