DPPH assay of the in-house marine-derived fungi uncovered that the EtOAc extract of the cultured fungus Aspergillus europaeus WZXY-SX-4-1, which was isolated from the marine sponge Xestospongia testudinaria, possesses radical scavenging activity. Chromatographic separation of the bioactive extract resulted in the isolation of 20 polyketide derivatives, including six new compounds namely eurobenzophenones A-C (1-3), euroxanthones A-B (4-5), and (+)1-O-demethylvariecolorquinones A (6). The structures of new compounds were determined on the basis of the analyses of spectroscopic data, including the Snatzke method for the configurational assignment. Benzophenones 3, 9 and 10 exhibited potent radical scavenging activity against DPPH. All polyketides were evaluated for the inhibitory effects toward the LPS induced nitric oxide (NO) production in mouse microglia BV2 cells and the NF-κB activation in human colon carcinoma cell line SW480. Compound 9 with the significant DPPH radical scavenging activity is corresponded to the potent inhibition against NF-κB in SW480 cells induced by LPS. Compounds 2, 4, 16-18 exerted remarked down-regulation of NF-κB in LPS-induced SW480 cells with weak inhibitory effects against NO production and the DPPH radical scavenging activity.