Previous reports reveal that Isoliquiritigen(ISL), a licorice flavonoid, possesses various antitumour properties, cyclophosphamide, an alkylating agent, has various genotoxic and carcinogenic effects, and to be involved in some secondary neoplasmas. However, it is still used extensively as an antitumour agent and immunosuppressant in the clinic. In order to find out whether isoliquiritigen could enhance antitumour activity, as well as decrease genotoxic effects of cyclophosphamide or not, the antitumour activity and genotoxic effect of oral intake of ISL combined with intraperitoneal injection of cyclophosphamide was investigated. Mice bearing mouse sarcoma S180 cells and cervical cancer U14 cells were respectively used to estimate the antitumour activity in vivo. The clastogenic activity in bone marrow polychromatic erythrocytes was assayed by frequency of micronucleus. The DNA damage in peripheral white blood cells was assayed by single cell gel electrophoresis. The results indicated that oral administration of ISL (5, 10 and 20 mg/kg body weight) alone has no obvious antitumour activity and genotoxic effect in mice, while ISL synergistically enhanced the antitumour activity of cyclophosphamide (40 mg/kg body weight) in a dose-dependent manner. in addition, ISL can decrease the micronucleus formation in polychromatic erythrocytes and DNA strand breaks in white blood cells in a dose-dependent way. Our results suggested that ISL is able to enhance the antitumour activity and decrease the genotoxic effect of cyclophosphamide.