Recent reports have raised concerns about the risk of skin cancer due to long-term use of UV nail-polish dryers, which emit Ultraviolet A light. However, the impact of this radiation on mammalian cells has not been fully understood. This study investigated the effects of a UV nail-polish dryer on mammalian cells and found that it led to the production of reactive oxygen species, causing damage to DNA and mitochondrial dysfunction. The analysis of somatic mutations revealed that the exposure to the UV radiation resulted in an increased number of specific DNA substitutions associated with reactive oxygen species. The research demonstrates that UV nail-polish dryers can induce DNA damage and mutations in various cell types, including primary mouse embryonic fibroblasts, human foreskin fibroblasts, and human epidermal keratinocytes.