Curcumin is the active ingredient of turmeric which is widely used as a yellow spice and food additive in Asia, India and western world. It is a complex natural extraction with various biological target points and different cellular activities including anti-inflammation, antioxidant, decreasing blood lipid, regulating human immunity function and antitumor effect. Recently, its anti-tumor mechanisms have been thoroughly investigated. Accumulating evidences show that curcumin holds a promising efficacy at very low concentration through its interaction with multiple molecular targets. In a phase 2 study, the clinical benefits of curcumin as a single agent were significant in patients with advanced pancreatic cancer. The present review delineates the molecular mechanism of the anti-tumor activities of curcumin in hematological malignancies. Our research shows that the multiple and broad biological effects of curcumin are mediated through its interaction with target proteins including cell proliferation pathway(p27KIP1, p21WAF1, pRbp- and cyclinD3), cell survival pathway (Mcl-1, Bax, Bak and STAT3,5), caspase activation pathway(caspase-8,caspase-9) and angiogenesis pathway( VEGF,VEGFR), as well as epigenetic modulation of target genes through interaction with histone deacetylases and histone acetyltransferases in hematological malignancies.