Flavonoids exhibit a wide spectrum of biological activities that can lead to beneficial effects for human health. The search for cytotoxic, genotoxic and/or antimutagenic natural compounds is therefore of great relevance, especially in cancer chemotherapy. In view of this, we screened the potential genotoxicity/antigenotoxicty of licoflavone C (LFLC) – a naturally occurring prenyl-flavone extracted from Genista ephedroides – using the micronucleus (MN) assay on stimulated and cytochalasin B-blocked human lymphocytes. LFLC did not increase the spontaneous MN level up to 600 µM final concentration where a strong toxicity was seen to occur. We therefore performed an antigenotoxicity assay against the two mutagenic anticancer drugs, mitomycin C (MMC) and daunorubicin (DAU), using two non-toxic LFLC concentrations (0.1 µM and 1.0 µM). The MN frequencies induced by 0.025 µg/ml or 0.05 µg/ml DAU were significantly lowered by 45.4% or 46.6% and 41.8% or 44.8% at LFLC 0.1 and 1.0 µM, respectively. After treatment with 0.085 µg/ml or 0.17 µg/ml MMC, we detected a reduction in genotoxicity of 35.1% or 37.0% and of 38.0% or 35.8% at LFLC 0.1 and 1.0 µM, respectively. In conclusion, LFLC was proven to be protective toward the chromosome damage induced by DAU or MMC in cultured human peripheral lymphocytes. Copyright © 2008 John Wiley & Sons, Ltd.