Rutin, due to its polyphenolic structure reveals antioxidant properties and may be used as a cytoprotective compound against UV-induced effects on skin cells. Therefore, the aim of this study was to examine the rutin effects on UV-induced changes in proteome profile of human skin fibroblasts cultured in vitro. PCA analysis of results obtained by QExactive OrbiTrap mass spectrometer show clear differentiation only between control and UVA treated cells, although significant changes in the individual proteins level are also observed between the rest of tested fibroblast groups. Rutin treatment prevents UVA-induced, even 2-fold, increase in the total expression of proteins involved in antioxidant (e.g. superoxide dismutases, disulfide isomerase) and inflammatory response (e.g. IL-17, PAK2, YWHAZ), what is not observed in fibroblasts after rutin treatment following UVB irradiation. However, rutin treatment of fibroblasts after UVB radiation promotes rutin-Keap1 adducts formation thus activation of Nrf2 - responsible for cytoprotective proteins synthesis. Rutin also prevents UV-induced apoptosis, through restoring the pro-apoptotic proteins level (e.g. p53 and cytochrome c) that is enhanced after the irradiation. In conclusion, our results show that rutin effectively prevents UV-induced damages associated with proinflammatory/prooxidative and proapoptotic activity.