By　inspiration　of　significant　anti-cancer　activity　of　our　previously　screened　natural　ergosterol　peroxide　(EP),　a　series　of　novel　steroidal　5　alpha,8　alpha-endoperoxide　derivatives　5a-d　and　14a-f　were　designed,　synthesized,　and　biologically　evaluated　for　their　in　vitro　anti-proliferative　inhibitory　and　cytotoxic　activity.　The　results　revealed　that　most　of　these　compounds　showed　moderate-to-excellent　anti-proliferative　effects　against　the　tested　cancer　cell　lines　(i.e.　HepG2,　SK-Hepl,　MDA-MB-231　and　MCF-7).　Among　them,　compound　5b　and　14d　exhibited　preferable　inhibitory　activities　(IC50　of　5b　and　14d　are　8.07　and　9.50　mu　M　against　HepG2,　respectively).　The　structure　activity　relationships　indicated　that　incorporation　the　peroxidic　bridge　to　the　steroid　scaffolds　at　C-5　and　C-8　positions　together　with　the　aliphatic　side-chain　at　the　C-17　position　would　provide　synergistic　effect　for　the　bioactivity.