Human skin-derived precursor cells are a multipotent stem cell population that resides within the dermis throughout adulthood. Human skin-derived precursor cells can be isolated, purified, and expanded in large quantities from any patient, in health and disease, and differentiated to mesodermal and ectodermal cell types. Recently, it was also found that they can be directed towards hepatic cells with acquired properties of toxicological relevance. As such, they represent a valuable cell source for the further development of human-relevant in vitro models for the identification and quantification of hepatotoxic compounds. In this chapter, a robust basic methodology to isolate, expand, and differentiate human skin-derived precursor cells into hepatic cells in a sequential and time-dependent way is provided.