Fusarium oxysporum is a widespread necrotrophic plant pathogen. Its infection affects several crop plants such as potato, tomato, cotton, banana, coffee, strawberry and sugarcane. The fungus produces oxalic acid, which triggers apoptosis in plants by a reactive oxygen species-dependent mechanism. Tobacco plants were genetically modified to express a gene coding for the enzyme oxalate descarboxilase (OxDc), isolated from Flammulina velutipes. The transgenic plants showed tolerance to Fusarium oxysporum. Even under lower expression of the gene, plants were able to control F. oxysporum infection. Thus, we demonstrated that the expression of the oxdc gene is a good alternative for the development of F. oxysporum resistant crops.