Three novel azaphilone alkaloids, namely chaetomugilides A–C (1–3), together with three related compounds (4–6) were isolated from the methanol extract of Chaetomium globosum TY1, an endophytic fungus isolated from Ginkgo biloba. Their structures were elucidated on the basis of extensive 1D and 2D NMR as well as HRESI-MS spectroscopic data analysis. The isolated compounds exhibited highly cytotoxic activities against human cancer cell line HepG2 with the IC 50 values range from 1.7 to 53.4 μM.