Pilosocereus gounellei (Cactaceae) is used to treat wounds and inflammation. In this study, we evaluated whether the saline extract from its stem would have genotoxic or anti-genotoxic effects. In the genotoxicity evaluation, mice received the extract (500, 1,000, or 2,000 mg/kg) orally while negative and positive controls were treated with saline solution (0.9% NaCl) per os and cyclophosphamide (CPA, 80 mg/kg i.p.), respectively. In the antigenotoxicity assay, using other animals, treatments were carried out by administering the extract (500, 1,000 or 2,000 mg/kg) or saline solution (negative control) per os and then CPA (80 mg/kg i.p.) 1 h later. Genotoxic effects were evaluated by micronucleus test and comet assay using peripheral blood and bone marrow cells. Oral administration of only the extract at 500 and 1,000 mg/kg did not result in genotoxicity. A slight increase in the incidence of micronucleus was observed at the highest dose (2,000 mg/kg). Administration of the extract before CPA reduced the micronucleated polychromatic erythrocytes (MNPCE) number by 49.07-71.43%, and DNA fragmentation in peripheral blood (85.04-94.44%) and bone marrow (87.43-92.70%) cells also decreased. In conclusion, when administered orally at the tested doses, the extract is genotoxically safe, being cautious in doses above 1,000 mg/kg, and has a protective effect against CPA-induced DNA damage.