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Objective:To investigate the cytotoxicity and the genotoxicity of standardized aqueous of dry leaves ofErythroxylum cuneatum(E. cuneatum) in humanHepG2 andWRL68 cells. Methods:The cytotoxicity ofE. cuneatum extract was evaluated by bothMTS andLDH assays. Genotoxicity study onE. cuneatum extract was assessed by the single cell gel electrophoresis (comet assay).The protective effect ofE. cuneatum against menadione-induced cytotoxicity was also investigated.Results:Results from this study showed thatE. cuneatum extract exhibited cytotoxic activities towards the cells withIC50 value of(125±12) and(125±14) μg/mL forHepG2 andWRL68 cells respectively, after72 h incubation period as determined byMTS assay.LDH leakage was detected at(251±19) and(199.5±12.0) μg/mL forHepG2 andWRL68 respectively. Genotoxicity study results showed that treatment withE. cuneatum up to1 mg/mLdid not cause obviousDNA damage inWRL68 andHepG2 cells.Addition ofE. cunaetum did not show significant protection towards menadione inWRL68 andHepG2Cells.Conclusions:E. cuneatum standardized aqueous extract might be developed in order to establish new pharmacological possibilities for its application.