Four new polycyclic polyprenylated acylphloroglucinol type metabolites, hypercohones D–G (1–4), along with four known analogues (5–8), were isolated from the aerial parts of Hypericum cohaerens. The structures of these isolates were elucidated by extensive spectroscopic methods. The inhibitory activities of these isolates against five human cancer cell lines in vitro were also tested.