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In vitro anticancer activity of the 80% ethanolic extracts of 23 traditionally used Ethiopian medicinal plants was studied using cervical (HeLa) and prostate (PC3) cancer cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) colourimetric assay. Mouse embryonic fibroblast normal cells(3T3) were used for evaluation of safety of extracts. Among the tested plants, Dovyalis abyssinica, Scadoxus multiflorus, Rumex abyssinicus, and Euphorbia abyssinica exhibited significant anticancer activity against HeLa cells with IC50 values of 6.2, 14.6, 18.6, and 22.8 µg/ml, respectively. Similarly, S. multiflorus and D. abyssinica significantly inhibited PC3 cell growth with IC50 values of 9.8 and 17.4 µg/ml, respectively. Extracts of S. multiflorus, R. abyssinicus, and E. abyssinica demonstrated high selectivity index. D. abyssinica showed selective toxicity against HeLa (SI = 2.51) cancer cells, but not against PC3 (SI = 0.98) cancer cells. Evaluation for safety indicated that about 83.3% of the extracts under this study were nontoxic at 30 µg/ml. The findings of this study suggest that further bioactivity guided fractionation and phytochemical studies may lead to the discovery of novel anticancer compounds.