Background: Recent studies have demonstrated that particulate matter (PM) induces oxidative stress and inflammatory reactions, and may cause certain skin diseases. Afzelin is a flavonoid isolated from Thesium chinese Turcz, which has anti inflammatory, anticancer and antibacterial properties. Objectives: This study aimed to investigate if afzelin affected inflammatory responses in human keratinocytes exposed to PM. Methods: HaCaT cells were treated with PM (25 μg/cm²) in the presence or absence of afzelin (200 μM). Cell viability was assessed using the water-soluble tetrazolium salt-1 assay. The generation of reactive oxygen species (ROS) was measured using the dichloro-dihydrofluorescein diacetate assay. Gene and protein expression were investigated using reverse transcription-quantitative polymerase chain reaction and western blot analysis. Levels of inflammatory cytokines were measured using ELISA. Results: Afzelin inhibited PM-induced proinflammatory cytokine mRNA expression and protein secretion in HaCaT cells. In addition, afzelin suppressed PM-induced intracellular ROS generation, and p38 mitogen-activated protein kinase and transcription factor activator protein-1 component c-Fos and c-Jun activation. Conclusion: In this study, the results suggest that afzelin exerts anti-inflammatory and antioxidant effects in PM-exposed HaCaT. Afzelin may have potential for preventing PM-induced inflammatory skin diseases.