Penisarins A (1) and B (2), sesquiterpene coumarins with an unusual tricyclic sesquiterpene system, were isolated from endophytic Penicilliumsp. KMU18029. Their structures were elucidated on the basis of spectroscopic methods, single-crystal X-ray diffraction, and electronic circular dichroism calculations. Compound 2showed significant cytotoxicities against two human cancer cell lines, HL-60 and SMMC-7721, with IC50values of 3.6 ± 0.2 and 3.7 ± 0.2 μM, respectively.