BACKGROUND Baicalin is a flavone isolated from the root of Scutellaria baicalensis and is used in traditional Chinese medicine. Psoriasis is a persistent and recurrent chronic inflammatory skin disease that is characterized by inflammation and increased proliferation of keratinocytes. This study aimed to investigate the effects of baicalin on HaCaT immortalized human keratinocytes in vitro and the molecular mechanisms involved. MATERIAL AND METHODS HaCaT keratinocytes were cultured in increasing concentrations of baicalin at 6.25 μM, 12.5 μM, and 25 μM. The in vitro model of psoriasis was established using HaCaT cells treated with tumor necrosis factor-alpha (TNF-alpha). The MTT assay was used to asses cell viability and apoptosis. Western blot was used to measure the expression of Bcl-2, Bax, pro-caspase-3, and cleaved caspase-3, and enzyme-linked immunosorbent assay (ELISA) was performed to detect inflammatory cytokines. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect the levels of STAT3 and p65 mRNA. RESULTS Baicalin reduced cell viability and induced apoptosis of HaCaT human keratinocytes in a dose-dependent manner. Increased cell viability and the expression of inflammatory cytokines by HaCaT cells induced by TNF-alpha were significantly inhibited by baicalin. Baicalin significantly inhibited the activation of the STAT3/NF-kappaB pathway in HaCaT cells stimulated by TNF-alpha. CONCLUSIONS Baicalin inhibited the proliferation and expression of inflammatory cytokines in HaCaT immortalized human keratinocytes in vitro through the inhibition of the STAT3/NF-kappaB signaling pathway.