With the decrease in land resources, marine resources open a new path for drug development, among which sponge is one of important marine biological resources. In recent years, many anti-tumor active compounds in new structures have been extracted and isolated from sponges. Targeted anti-tumor drugs from sponge become a new trend during the development of innovative drugs of marine resources. This essay summarizes the anti-tumor mechanism of sponge's active compounds and its related synthetics on the basis of its various anti-tumor targets including cytoskeleton (microtubule and actin), protein kinases (cyclin dependent kinase and aurora kinase), DNA synthesis and relevant enzymeso, growth microenvironment for tumor tissues and the immune system. Additionally, it also briefs relevant clinical studies.