Zinc phenolsulfonate is used as an astringent cosmetic ingredient at a maximum concentration of 2% in leave-on products in Europe and Korea. It is widely incorporated into cosmetic formulations such as deodorants and baby lotions; however, no data are currently available regarding its percutaneous absorption. As the percutaneous absorption rate is a critical parameter in risk assessment, experimental evaluation through in vitro studies is essential. Prior to conducting absorption studies, analytical methods were developed for the quantitation of zinc phenolsulfonate in swab (SW), stratum corneum (SC), skin (dermis + epidermis, SK), and receptor fluid (RF) matrices. The developed methods demonstrated excellent linearity (r² = 0.9974–0.9999), accuracy (88.0–112.2%), and precision (1.9–10.0%) in accordance with validation guidelines. Percutaneous absorption was determined using a Franz diffusion cell with mini-pig skin. Lotion formulations containing zinc phenolsulfonate (1% and 2%) were applied to the skin at 10 mg/cm², and samples were analyzed by liquid chromatography–mass spectrometry (LC–MS/MS) after 24 hours. The total percutaneous absorption rates of zinc phenolsulfonate were 20.3 ± 7.3% and 18.8 ± 7.0% for the 1% and 2% lotion formulations, respectively. These findings provide essential data for exposure estimation and risk assessment of cosmetics containing zinc phenolsulfonate.