This work demonstrates the toxic effects of Sinularia leptoclados. Sinularia depressan and Sinularia inflate extracts on human oral squamous cell carcinoma (SCC4, SCC9 and SCC25) cells using cell adhesion and cell viability assays. The three extracts inhibited growth of human SCC25 (which exhibited effective differentiation) cells than they did SCC4 (moderate differentiation) and SCC9 (poor differentiation) cells. The morphological changes of the SCC25 cells upon treatment with the three extracts were caused by apoptosis, as determined from the morphological features (spheroid shape, chromatin condensation and formation of apoptotic bodies). Flow cytometry indicates that three extracts sensitized SCC25 cells in the G2/M phases with a concomitantly and significantly increased fraction of sub-G1. This investigation reveals that apoptosis that occurred when the SCC cells were treated with S. leptoclados, S. depressan and S. infllate extracts was accompanied by up-regulation of p53 and activation of caspase-3 expression.