Helianthus annuus seed byproduct is a residual product obtained after seed oil extraction. The present study investigated the preventive and repair effects of the H. annuus seed byproduct ethanol extract (HSE) on ultraviolet radiation (UVR)‐induced injury in human immortalized keratinocytes (HaCaTs) and human skin fibroblasts (HSFs). Results revealed that the total phenolic acid and oligosaccharide content in HSE was >50%. HSE had a stronger preventive effect on UVR‐induced injury than the repair effect. Moreover, phenolic acids were the main active component of HSE mediating the preventative effect. In HaCaTs and HSFs, HSE prevented UVR‐induced injury by inhibiting excessive ROS production. It reduced the secretion of tumor necrosis TNF‐α, IL‐1α, IL‐1β, IL‐6, and IL‐8 by inhibiting the level of ROS, thus reducing inflammation‐mediated injury to skin cells. In addition, HSE inhibited the expression of various mRNA kinases in the MAPK–ERK/p38/JNK pathway. This downregulated the expression of activator protein‐1 (AP‐1) mRNA and further reduced the secretion of matrix metalloproteinase (MMP)‐1, MMP‐3, and MMP‐9 as well as reduced UVR‐induced injury to the cells. In conclusion, HSE is a broad‐spectrum, natural UV filter with high efficiency and low toxicity that has the potential to be used in sunscreen products.