Reishi mushroom Ganoderma lucidum is commonly used in conventional medicine due to its high medicinal properties. Phytochemical screening of G. lucidum mushroom extract found to be flavonoids, glycosides, terpenoids, phenols, Carbohydrates. The current study was applied to demonstrate the In vitro cytotoxicity of ethanolic extract of G. lucidum mushroom against two human cell lines breast cancer cell line MCF-7 and human embryonic liver cell line WRL-68. The measured inhibitory concentration fifty(IC50) values were observed maximum dose responses (IC50) of WRL68 and MCF-7 at 2.0 µg/ml ethanolic mushroom concentration reported of 210.2% and 185.1% compared to the dose-response (IC50) of antidrug doxorubicin (control) at 2.0µg/ml ethanolic mushroom concentration counted to be 18.68. The highly cytotoxic activity of the extract on cell viability MCF-7 and WRL-68 were generally observed 100% and 97% at extract concentrations of 12.5 µg/ml and 25µg/ml respectively compared to antidrug was determined to be 94% cell viability at 6.25 µg/ml concentration.