Vismodegib (Erivedge®, Genentech) is a first-in-class inhibitor of the hedgehog signaling pathway for the treatment of basal cell carcinoma (BCC). The treatment currently consists of the oral administration of Erivedge® capsules. Although it has shown therapeutic efficacy in clinical trials, there are many side effects related to its systemic distribution. In this work, we have incorporated vismodegib to ultradeformable liposomes in order to obtain a nano-drug delivery system via topical route, which could be useful to reduce systemic distribution -and consequently side effects- while achieving a viable epidermis-specific target where neoplastic events of BCC develop. Vismodegib was loaded into liposomes composed of soy phosphatidylcholine and sodium cholate, and the obtained formulation was characterized by different techniques, both experimental and computational. Several analyses were performed,with a special focus on the interaction of the drug with the liposomal membrane. Additionally, the penetration of Vismodegib delivered by ultradeformable liposomes was assessed on human skin explants. This is one of the first works that propose the topical route for Vismodegib and the first, to our knowledge, in stabilizing this active into a nano-drug delivery system specifically designed for penetrating the stratum corneum impermeable barrier.