Background/Aim: COVID-19 pandemic caused the rapid dissemination of ultraviolet C (UVC) sterilization apparatuses. Prolonged exposure to UVC, however, may exert harmful effects on the human body. The aim of the present study was to comprehensively investigate the anti-UVC activity of a total of 108 hot-water soluble herb extracts, using human dermal fibroblast and melanoma cell lines, for the future development of skin care products. Materials and Methods: Exposure time to UVC was set to 3 min, and cell viability was determined using the MTT assay. Anti-UVC activity was determined using the selective index (SI), a ratio of 50% cytotoxic concentration for unirradiated cells to 50% effective concentration that restored half of the UVC-induced decrease of viability. Results: Dermal fibroblasts at any population doubling level were more resistant to UVC irradiation than melanoma cells. Both 49 herb extracts recommended by Japan Medical Herb Association (JAMHA) and 59 additional herb extracts showed comparable anti-UVC activity. SI values of selected herbs (Butterbur, Cloves, Curry Tree, Evening Primrose, Rooibos, Stevia, Willow) were several-fold lower than those of vitamin C and vanillin. Their potent anti-UVC activity was maintained for at least 6 h post irradiation, but declined thereafter to the basal level, possibly due to cytotoxic ingredients. Conclusion: UVC sensitivity may be related to the growth potential of target cells. Removal of cytotoxic ingredients of herb extracts may further potentiate and prolong their anti-UVC activity.SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection caused the coronavirus disease of 2019 (COVID-19) pandemic, accompanied by serious morbidity and mortality (1). This triggered the rapid dissemination of various types of ultraviolet C (UVC) sterilization apparatuses in hospital emergency department waiting rooms, clinics, nursing homes, prison common areas, public libraries (providing the sterilization box for cleaning books), schools, restaurants, and bedrooms (2). While UVC has strong bactericidal (3) and virucidal (4) activity, the prolonged exposure to UVC may have harmful effects on the human body, causing various diseases such as skin cancer (5) and cataracts (6). Therefore, the search for nontoxic UVC protective substances is crucial. Sakagami et al. recently reported that (i) human normal cells (gingival, periodontal, and dermal fibroblasts and pulp cells] are generally resistant to UVC irradiation, as compared with human cancer cell lines (oral squamous cell carcinoma, lung cancer, glioblastoma, leukemia, and melanoma) (7); and that (ii) 1540