Small interfering RNA (siRNA)-based therapeutics represent a novel and compelling drug modality, provided that safe and competent vectors are available for their delivery. Here, we report a biodegradable amphiphilic poly(aminoester) dendrimer for effective siRNA delivery. This dendrimer is readily biodegradable upon enzyme action, and harnesses the delivery features of both lipid and polymer vectors thanks to its lipid/dendrimer hybrid structure. This study opens new perspectives for developing biodegradable and biocompatible vectors for siRNA therapeutics.