In the present work, ZnFe₂O₄ nanopowder, as a highly efficient and heterogeneous catalyst, was prepared and fully characterized by IR, UV, XRD, EDX and SEM analysis. The nanocatalyst was employed as a highly stable and reusable catalyst for the synthesis of pyrano[2,3-d]pyrimidines by the one-pot three-component condensation reaction of 1,3-dimethylbarbituric acid and malononitrile with aromatic aldehydes under solvent-free conditions. ZnFe₂O₄ nanoparticles with Lewis acidic properties (by the Fe³⁺ of Fe₂O₃) and basic character (related to the O²⁻ of ZnO), can catalyze this reaction. This procedure has some advantages, such as efficiency, generality, high yield, short reaction time, cleaner reaction profiles, ease of product isolation and simplicity.