Fusion molecules composed of a type I interferon protein or portion thereof and a type III interferon protein or portion thereof, pharmaceutical compositions containing the fusion molecules, and methods for their use in inhibiting infection, inhibiting or treating cancer, inducing signaling of transcription of IFN-stimulated genes through an IFN-αR2 chain in a subject suffering from an infection which degrades or downregulates an IFN-αRl chain, and treating various diseases or conditions are provided.