The present study is designed to investigate the local delivery of Cisplatin in cutaneous epithelial malignancies from protransfersome. Cisplatin-loaded protransfersome was prepared and characterized for size, zeta potential, surface morphology, percentage drug entrapment, in vitro drug permeation, vesicle-skin interaction, drug-excipients interaction, and stability study. An in vivo study was also performed to evaluate the efficacy of the proposed system. The size of the system was found to be $1115.56{pm}254$ nm with zeta potential of -61.1 mV. Morphological studies revealed the defined structure of vesicles. The percentage entrapment of Cisplatin was found to be $97.97{pm}1.95%$ with skin permeation data of $560.20{pm}7.89{mu}g/cm^2$. The presence of a fluorescence marker in the skin showed better skin penetration ability of the protransfersome. On comparison with IR spectra, it was clear that there was no significant interaction between the encapsulated drug and the excipients. In vivo performance of the system showed an increase in the therapeutic efficacy of drug with less systemic toxicity. The findings of the work appear to support improved, site-specific, and localized drug action, thus providing a better option to deal with skin-cited problems like squamous cell carcinoma. Further, the ultra-deformable nature of system seems to permit better delivery of the drug at the tumor site.