Therapies for the treatment of Chronic Myeloid Leukemia and other leukemias are still limited for patients at advanced stages, which allow development of point mutations in the BCR-ABL fusion gene that render CML cells insensitive to therapies. An effective non-viral delivery system based on lipopolymers is described in this study to deliver specific siRNAs to CML cells for therapeutic gene silencing. The lipopolymer, based on the lipid α-linolenic acid (αLA) substitution on low molecular weight polyethyleneimine (PEI), was used to deliver siRNA against the BCR-ABL gene and, the resultant therapeutic effect was evaluated in in vitro and in vivo CML models. The study concluded that siRNA/PEI-αLA nanoparticles enabled silencing of the BCR-ABL gene and BCR-ABL protein, which consequently reduced growth on CML K562 cells in vitro and arrested the growth of localized tumors in a localized CML mouse model. The results from this study confirmed the potential use of lipopolymers as delivery systems and are encouraging for the future design of non-viral delivery systems for the treatment of CML and other hematological malignancies resulting from gene fusions.