A series of twenty-two monosubstituted N-aryl-4-hydroxyquinoline-3-carboxanilides designed as dual anti-invasive agents was prepared and characterized. Lipophilicity significantly affects biological activities of compounds and ADME properties, therefore the lipo-hydrophilic properties of these 4-hydroxyquinoline-3-carboxanilides were investigated. All the derivatives were analyzed by reversed-phase high-performance liquid chromatography. The procedure was carried out under isocratic conditions with methanol as the organic modifier in the mobile phase using an end-capped non-polar C18 stationary reversed-phase column. In this study, correlations between the logarithm of the capacity factor k and log P/Clog P values calculated by various methods are discussed, as well as the relationships between lipophilicity and chemical structure of the studied compounds.