Two new benzaldehyde derivatives aspergitones A (1) and B (2), along with eight known analogues 3-10, were isolated from the soft coral-associated epiphytic fungus Aspergillus sp. EGF 15-0-3. Their structures were elucidated using 1D and 2D NMR spectroscopy and HRESIMS, while the absolute configuration of 1 was determined through the experimental and computational ECD analysis. Based on the molecular docking and activity assays against the antitumor targets tyrosyl-DNA phosphodiesterases 1 and 2 (TDP1 and TDP2), compound 7 was found to be a potential dual inhibitor against TDP1 and TDP2, while 5 showed the strongest inhibition against TDP1.