Surgical site infections (SSIs) represent an important clinical problem associated with increased levels of surgical morbidity and mortality. UVC irradiation during surgery has been considered to represent a possible strategy to prevent the development of SSI. 254-nm UVC induces marked levels of DNA damage by generating cyclobutyl pyrimidine dimers (CPD) in microorganisms. However, this effect is elicited not only in microorganisms, but also in human cells, and chronic exposure to 254-nm UVC has been established to represent a human health hazard. In contrast, despite short wavelength-UVC light, especially 222-nm UVC, having been demonstrated to elicit a bactericidal effect, single irradiation with a high dose of 222-nm UVC energy has been reported to not induce mutagenic or cytotoxic DNA lesions in mammalian cells. However, the effect of chronic irradiation with a high dose of 222-nm UVC to mammalian cells has not been determined. In this study, it was demonstrated that large numbers of CPD-expressing cells were induced in the epidermis of mice following treatment with a small amount of single exposure 254-nm UVC, and then less than half of these cells reduced within 24 h. Chronic 254-nm UVC irradiation was revealed to induce sunburn and desquamation in mouse skin. Histological analysis demonstrated that small numbers of CPD-expressing cells were detected only in hyperkeratotic stratum corneum after chronic irradiation with a high dose of 254-nm UVC, and that significant hyperplasia and intercellular edema were also induced in the epidermis of mice. In contrast, chronic irradiation with 222-nm UVC light was revealed not to induce mutagenic or cytotoxic effects in the epidermis of mice. These results indicated that 222-nm UVC light emitted from the lamp apparatus (or device), which was designed to attenuate harmful light present in wavelengths of more than 230 nm, represents a promising tool for the reduction of SSI incidence in patients and hospital staff.