Talasterone A (1), an unprecedented 6/6/5 tricyclic 13(14?→?8)abeo-8,14-seco-ergostane steroid, together with two known congeners dankasterone B (2) and (14β,22E)-9,14-dihydroxyergosta-4,7,22-triene-3,6-dione (3), were characterized from Talaromyces adpressus. The structure of 1 with absolute configuration was elucidated based on NMR spectroscopic data and ECD calculation. Compound 2 belongs to a class of unconventional 13(14?→?8)abeo-ergostanes, which have been renewed via the 1,2-migration of C-13-C-14 bond to C-8. In addition, compound 1 represents the first example of ergostane with a tricyclic 13(14?→?8)abeo-8,14-seco-ergostane skeleton. The proposed biosynthetic pathway was established with the support of the coisolation of the known congeners from the producing organism. It is especially noteworthy that compound 1 exhibited potent anti-inflammatory activity with an IC₅₀ value of 8.73?±?0.66?μM, inhibiting the NF-κB pathway and thus reducing the production of proinflammatory cytokines.