A critical step to escape from the carcinogenic potential of UV radiation is mediated by the protein p53. P53 activates growth arrest, allowing for DNA repair, which removes damaged cells. The concept of photoprotection involves blocking apoptosis and the prevention of oxidative damage to cellular DNA. Date seed oil (DSO) extract has been reported to be beneficial in the reduction of chemically induced oxidative stress in normal human skin. In this study, we investigated the DNA-protective qualities of DSO as measured by p53 expression in human skin biopsies, one day after exposure to ultraviolet B (UVB) radiation. P53 expression was analyzed using immunohistochemistry. The results showed an increase in p53 expression in the basal cell compartment of UVB-exposed skin as compared to the non-UVB-exposed skin. However, DSO has significant photoprotective effects by inhibition of damage caused by UVB irradiation: a significantly lower fraction of cells was p53 positive as compared to the non-DSO-treated skin. We conclude that p53 expression is a sensitive parameter for the detection of UVB-induced damage in the skin and suggest that DSO could provide an efficient complement to photoprotective measures and may contribute to reduce the DNA damage.