Nine new polyprenylated acylphloroglucinols (PPAPs), hyperattenins A-I (1-9), together with thirteen known analogues (10-22), were isolated from the aerial parts of Hypericum attenuatum Choisy. The structures of 1-9 were elucidated by extensive spectroscopic analysis. The absolute configuration of 1 was determined by a single X-ray crystallographic analysis, and the absolute configurations of 2-9 were determined by comparison of experimental and calculated electronic circular dichroism (ECD) spectra. Compound 1 was characterised as a bicyclo[3.3.1] nonane derivative containing an unusual hemiacetal functionality formed by a series of redox reactions on its side chains, which occurs rarely in nature. All new isolates were evaluated for cytotoxic activities against several human cancer cell lines. Compound 9 exhibited significant inhibitory activity against the HL-60 and A-549 cell lines, with IC50 values of 2.04 and 3.26 mu M, respectively. Compound 9 also showed low toxicity to Beas-2B cells (IC50 = 14.36 mu M), suggesting that it could be a selective anti-tumour agent for leukaemia and lung cancer. Compounds 2-8 were also screened for their anti-HIV-1 activities.