The therapeutic potentials of 14-acetoxy-7β-(3’-ethyl cis-crotonoyloxy)-1α-(2’-methylburyryloxy)-notonipetranone (AECN), a sesquiterpenoid seperated from Tussilago farfara, for the psoriasis were investigated in the immortalized human keratinocyte cell line (HaCaT cells). Treatment of AECN upregulated the ARE-luciferase activity dose-dependently, showing 21.6-fold increase at 2.5 μM. Also, it induced the protein expression of Nrf2 and its downstream target, heme oxygenase-1. In addition, AECN treatment increased the nuclear translocation of Nrf2, suggesting that AECN activates Nrf2 pathway. To identify whether AECN could inhibit the activation of STAT3 and NF-κB, crucial transcription factors involved in the pathogenesis of psoriasis, we conducted western blot analysis and luciferase assay. AECN inhibited IL-6-induced STAT3 phosphorylation and STAT3-dependent transcriptional luciferase activity, and also suppressed TNF-α-induced NF-κB activation. Moreover, TNF-α-induced mRNA levels of IL-17, IL-17A, IL-23, and TNF-α were reduced, suggesting the potency of AECN to decrease inflammatory mediators regulated by NF-κB activation. Proliferation assay revealed that 2.5 μM AECN inhibited IL-6-induced hyperproliferation of HaCaT cell and the mRNA expression of cyclin d1, one of the markers for proliferation. Taken together, these results indicate that AECN, as an effective Nrf2 activator, can be a promising therapeutic candidate for treatment psoriasis through inhibition of STAT3 and NF-κB activation.