The properties of flexographic inks obtained by the partial replacement of nitrocellulose (NC) resin with different amounts of polyurethane (PU) resins were evaluated for the statistical planning of mixtures to develop an optimum ink formulation. The formulations were developed using a statistical tool and they were found to present properties predicted by the tool. The results indicate that the substitution of the NC resin with PU resins leads to increased resistance of the ink film to delamination. The system obtained with the partial substitution of NC with PU has higher lamination bond strength than the pure NC‐based system. The ink films of the formulations NC‐based and NC/PU‐based were evaluated by spectroscopy UV–vis, both inks have similar transparency of greater than 95% above 575 nm. When exposed to water, milk, and UV light, ink surfaces showed similar behavior in the atomic force microscope, Fourier‐transform infrared spectroscopy, and UV–vis analysis. However, ink formulations with higher PU contents underwent higher photodegradation. Other properties such as the viscosity ink, gloss, coating strength, color, adhesion, and blocking of the NC/PU‐based ink film did not vary significantly when compared to those of the standard ink produced exclusively with NC resin.