Polyoxometalates have attracted much attention in the field of medicine because of their good bioactivities, including antitumor, antibacterial and antivirus activities. With its unique characteristics in structure, polyoxometalates could be modified by introducing different types of organic or inorganic groups into their structure, to improve their stability and bioactivity. The synthesis of new polyoxometalates with high bioactivities and low toxicity is an issue widely studied. This paper reviews studies of polyoxometalates derivatives, the antitumor mechanism and the biological effects of polyoxometalates in recent years. Organic and organometallic derivatives have remarkable antitumor activities against several types of tumor cells. According to the oxidation-reduction theory, the antitumor activity of polyoxometalates is related with the oxidation-reduction property of polyanions, and the theory is well supported by many evidences. However, the nucleic acid degradation effect observed in the in vitro implies that polyoxometalates could suppress tumor growth by the interaction with DNA or RNA. Moreover, it is found that polyoxometalates have effects on apoptosis, autophagic cell death and the immune system in the process of tumor inhibition, where the apoptosis effect plays an important role in the antitumor activity of polyoxometalates.