The f subunit of the eukaryotic initiation factor 3 (eIF3f) is downregulated in several cancers and in particular in melanoma and pancreatic cancer cells. Its enforced expression by transient gene transfection negatively regulates cancer cell growth by activating apoptosis. With the aim to increase the intracellular level of eIF3f proteins and activate apoptosis in cancer cell lines, we developed a protein transfer system composed of a cell-penetrating peptide sequence fused to eIF3f protein sequence (MD11-eIF3f). To determine whether exogenously administered eIF3f proteins were able to compensate the loss of endogenous eIF3f and induce cancer cell death, we analyzed the therapeutic action of MD11-eIF3f in several tumor cells. We identified four cell lines respondent to eIF3f-treatment and we evaluated the antitumor properties of the recombinant proteins using dose- and time-dependent studies. Our results demonstrate that this protein delivery approach represents an innovative and powerful strategy for cancer treatment.