Cytochalasans are a large group of fungal alkaloids with tricyclic core, which consists of a macrocyclic ring (either a carbocycle, a lactone or a cyclic carbonate) and an isoindolone moiety. These fungal alkaloids are contributed by a polyketide backbone and an amino acid (either leucine, phenylalanine or tryptophan) with diverse bioactivities, such as antimicrobial, antiparasitic, cytotoxic, and phytotoxic activities [1]. Cytochalasan-producing fungi are derived from very diverse ecological settings, including from plant [1–5] and marine [1,6,7]. But there is no report that cytochalasan was found from the lichen-derived endophytic fungus. As part of our search for bioactive secondary metabolites from endolichenic fungi [8–13], the chemical investigation of the fungal strain Chaetomium globosum (No.64-5-8-2) was carried out, which led to the isolation of a new cytochalasan, chaetoglobosin Y (1), along with related six known cytochalasans, chaetoglobosin Fex (2) [6,14], chaetoglobosin E (3) [15], isochaetoglobosin D (4) [6], chaetoglobosin G (5) [15], cytoglobosin B (6) [6], and cytoglobosin C (7) [6] (Fig. 1). Their structures were determined by detailed spectroscopic analyses and comparison with those of the closely related compounds previously reported. The cytotoxicity to HCT-116 cell line of 2–7 was evaluated in vitro with doxorubicin as positive control.