Abstract A protocol for the synthesis of trisubstituted furans via phosphoric acid‐catalyzed regioselective cascade cyclization/amination of para ‐quinone methides ( p ‐QMs) with β ‐ketodinitriles has been disclosed for the first time. Various kinds of p ‐QMs and β ‐ketodinitriles can effectively produce the desired polysubstituted furan derivatives in 64–95% yields, demonstrating high atomic economy and their application in the construction of polysubstituted furan heterocycles. Preliminary biological activity assay suggests that these furans have potential anticancer activities.