Granulosane A (<b>1</b>), a new C<sub>27</sub> bishomoscalarane sesterterpenoid with a rare 6/6/6/8 tetracyclic skeleton, together with eight additional new C<sub>27</sub> bishomoscalarane sesterterpenes (<b>2</b>, <b>8</b>-<b>14</b>) and five new C<sub>26</sub> 20,24-bishomo-25-norscalarane sesterterpenes (<b>3</b>-<b>7</b>), were isolated from the marine sponge <i>Dysidea granulosa</i> collected in the South China Sea. Their structures were elucidated by extensive spectroscopic analysis and quantum chemical calculation methods. Compound <b>4</b> showed antiproliferative activities against two cancer cell lines.