A set of benzofuroxan derivatives was tested in vitro against Trypanosoma cruzi epimastigote forms. In order to continue the research on the potential of these compounds, the anti-T. cruzi activity of a series of twenty N0 -(benzofuroxan-5-yl)methylenebenzohydrazides was investigated in vitro. The use of the benzofuroxan system as a bioreductive pharmacophore and also as a cruzipain inhibitor has been described as an alternative in the search for new antichagasic drugs. The series was designed to explore the influence of physicochemical properties such as the electronic effect (s) and hydrophobicity (p), based on the Craig diagram. The influence of physicochemical properties on these benzofuroxan derivatives' activity was observed, and the presence of electron-withdrawing and hydrophobic groups attached to the benzene ring seems to make a favorable contribution at lower concentrations.