Background: Previous phytochemical studies of whole Vernonia cinerea L. plants have identified sesquiterpene lactones, sterols, and triterpenes, which possess anticancer, antifeedant, and antimalarial activities. However, there are no reports of other types of bioactive metabolites. Therefore, the present study aimed to identify phenolic compounds with anti-inflammatory activity in the aerial parts of the plant.Methods and Results:Compounds were isolated from the aerial parts of V. cinerea using a silica and C-18 gel columns and semipreparative HPLC instrument, and the structures of the compounds were determined using one- and two- dimension nuclear magnetic resonance spectroscopy and mass spectroscopy. The chloroform soluble extracts and isolated compounds were evaluated for their anti-inflammatory potential based on their ability to inhibit nitric oxide production and TNF-α induced NF-κB activity.Conclusions:Phytochemical study of the aerial parts of V. cinerea led to the isolation of six phenolic compounds. Compound 1 was a major metabolite, and to the best of our knowledge, compounds 2 - 6 were isolated from V.cinerea for the first time. Among the isolates, compounds 1 and 3 exhibited TNF-α-induced NF-κB activity with IC50 values of 7.5 and 11.5 M, respectively, and the inhibitory activity of phenyl propanoid compound 3 on TNF-α-induced NF-κB was evaluated for the first time.