A novel hybrid PKS-NRPS alkaloid, xylarialoid A ( 1 ), containing a 13-membered macrocyclic moiety and [5,5,6] fused tricarbocyclic rings, together with ten known cytochalasins ( 2 - 11 ), was isolated from a plant-derived endophytic fungus, Xylaria arbuscula . The chemical structures of all compounds were elucidated using 1D and 2D NMR, HR ESIMS spectroscopic analyses, and electronic circular dichroism (ECD) calculation. Compounds 1 - 3 and 10 exhibited significant antitumor activities against A549 and Hep G2 cell lines, with IC 50 values of 3.6-19.6 μM. In addition, compound 1 showed potent anti-inflammatory activity against LPS-induced nitric oxide (NO) production in macrophage RAW 264.7 cells (IC 50 , 6.6 μM).