Particulate matter (PM), a widespread airborne contaminant, is a complex mixture of solid and liquid particles suspended in the air. Recent studies have demonstrated that PM induces oxidative stress and inflammatory reactions, and may cause certain skin diseases. Afzelin is a flavonoid isolated from Thesium chinense Turcz, which has anti‑inflammatory, anticancer and antibacterial properties. Therefore, the present study aimed to investigate if afzelin affected inflammatory responses in human keratinocytes exposed to PM. HaCaT cells were treated with PM (25 µg/cm2) in the presence or absence of afzelin (200 µM). Here, standard reference material 1649b was used as PM. Cell viability was assessed using the water‑soluble tetrazolium salt‑1 assay. The generation of reactive oxygen species (ROS) was measured using the dichloro‑dihydro‑fluorescein diacetate assay. Gene and protein expression were investigated using reverse transcription‑quantitative polymerase chain reaction and western blot analysis, respectively. Levels of secreted inflammatory cytokines were measured using ELISA. The results suggested that 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. The results indicated that afzelin exerts anti‑inflammatory and antioxidant effects in PM‑exposed HaCaT. Afzelin may have potential for preventing PM‑induced inflammatory skin diseases.