Nine new ergosteroids (1-9) and seven known ones (10-16) were isolated from Talaromyces adpressus. Their structures and absolute configurations were determined by the interpretation of NMR spectroscopic data, HRESIMS, ECD calculations, and single-crystal X-ray diffraction analyses. Structurally, compound 1 was an ergosteroid with two epoxy and a 3α-OH group at ring A, while compounds 8 and 9 had a contracted ring A with a peroxy bridge between C-3 and C-9, which were reported for the first time. Compounds 2-6, 9, 11, and 15 displayed cytotoxic activities with IC50 values ranging from 0.4 to 32 μM, and compound 7 exhibited an immunosuppressive effect against LPS-induced B lymphocyte proliferation with an IC50 value of 8.6 μM. The structure-activity relationships of these compounds are briefly discussed.