Two new isoindolin-1-ones, named erinacerin (M–N) along with eleven known compounds have been isolated from the fruiting bodies of the medicinal mushroom Hericium erinaceus. The structures of compounds were elucidated based on spectroscopic studies and comparison with the known related ones. The anticancer potential of the isolates were tested with an in vitro cytotoxic assay against six human cancer cell lines (SH-SY5Y, 1321N1, HCT-116, Caco-2, OVK18 and HeLa).