AbstractLong-term exposure to air pollution has been associated with the development of some inflammatory processes related to skin. The goal of modern medicine is the development of new products with antiflammatory action deriving from natural sources to improve environmental and economic sustainability. In this study, two different humic acids (HA) were isolated from from lignite (HA-LIG) and composted artichoke wastes (HA-CYN) and characterized by infrared spectrometry, NMR spectroscopy, thermochemolysis-GC/MS, and high-performance size-exclusion chromatography (HPSEC), while their antiflammatory activity was evaluated on HaCaT cells. Spectroscopic results showing the predominance of apolar aliphatic and aromatic components in HA-LIG, whereas HA-CYN revealed a presence of polysaccharides and polyphenolic lignin residues. The HA application on human keratinocyte pre-treated with Urban Dust revealed a general increase of viability suggesting a protective effect of humic matter due to the content of aromatic, phenolic and lignin components. Conversely, the gene expression of IL-6 and IL-1β cytokines indicated a significant decrease after application of HA-LIG, thus exhibiting a greater antiflammatory power than HA-CYN. The specific combination of HA protective hydrophobic components, viable conformational arrangements, and content of bioactive molecules, suggests an innovative applicability of humic matter in dermatology as skin protectors from environmental irritants and as antiflammatory agents.