Cytotoxic effect of Discosoma sp., Isis hippuris and Nephthea chabrolii extracts on human oral squamous cell carcinoma SCC25 cells was investigated herein. The three marine extracts reduce the cell attachment and exhibit a dose-dependent cytotoxic effect. I. hippuris extract exhibited greater activity in inhibiting cell growth than Discosoma sp. and N. chabrolii. After cells were treated with three extracts, morphological alterations of cells such as rounding and membrane blebbing, nuclear condensation and apoptotic bodies are observed. The three extracts sensitized cells in the G0/G1 and S-G2/M phases with a concomitant significantly increased sub-G1 fraction, determined by flow cytometry. This apoptosis process was accompanied by up-regulation of Fas and activation of caspase-3 expression. These results imply that the three extracts caused apoptosis of SCC25 cells.