Granulosane A (1), a new C27 bishomoscalarane sesterterpenoid with a rare 6/6/6/8 tetracyclic skeleton, together with eight additional new C27 bishomoscalarane sesterterpenes (2, 8-14) and five new C26 20,24-bishomo-25-norscalarane sesterterpenes (3-7), were isolated from the marine sponge Dysidea granulosa collected in the South China Sea. Their structures were elucidated by extensive spectroscopic analysis and quantum chemical calculation methods. Compound 4 showed antiproliferative activities against two cancer cell lines.