UV light is considered one of the major etiological factor in skin aging, cancer and also to systemic impairment such as immunosuppression. Increased production of reactive oxygen species (ROS) and oxidative stress condition are known to play a central role in initiating and driving the signalling events that lead to cellular response following UV irradiation. In the present study we have investigated the photoprotective activity of a standardized extract from red orange (ROE), obtained from three red orange varieties and containing as main active principles phenolic compounds (anthocyanins, flavanones and hydroxycinnamic acids) and ascorbic acid. The aim of this study was to evaluate the efficacy of ROE in modulating cellular responses to UVB in human keratinocytes (HaCaT). Our data indicate that ROE is potentially able to efficiently counteract UVB-induced response, and in particular some events associated to inflammation and apoptosis, such as NF-kB and AP-1 translocation and procaspase-3 cleavage. This activity is probably due to a block of cellular oxidative stress-related events. Thus we can propose ROE as a useful natural standardised extract in skin photoprotection with promising applications in the field of dermatology.