The present study was undertaken to examine the effect of cerebrosides derived from the sea cucumber Acaudina molpadioides and the starfish Asterias amurensis on the anti-tumor activity in vitro and in vivo. The results indicated that both Acaudina molpadioides cerebrosides (AMC) and Asterias amurensis cerebrosides (AAC) exhibited an inhibitory effect on cell proliferation through induction of apoptosis in S180 cells. Moreover, administration of AMC and AAC (50 mg/kg BW) on S180 tumor bearing mice reduced the tumor weight by 45.24 % and 35.71 %, respectively. In S180 ascites tumor model, AMC and AAC (50 mg/kg BW) treatment exhibited a significant ascites fluid growth inhibition of 31.23 % and 22.72 %. Furthermore, the ascites tumor cell viability ratio in AMC and AAC groups reduced to 50.89 % and 51.69 %, respectively. The life span of AMC and AAC administrated groups increased by 55.28 % and 35.77 % compared to control. Quantitative real-time PCR analysis demonstrated that the administration of AMC and AAC down-regulated the expression of Bcl-2, Bcl-xL, while on the other hand, up-regulated Bax, Cytochrome c, caspase-9 and caspase-3 mRNA level of the S180 ascites tumor cells. It was concluded that AMC and AAC should have potential anti-tumor activity both in vitro and in vivo by inducing apoptosis through the mitochondria-mediated apoptosis pathway. AAC seemed to be more effective than AMC in vitro but less potent in vivo. It may depend on the structural differences in their fatty acid groups and sphingoid bases.