Extracellular 5'-nucleotidase (CD73) is not only highly expressed in a variety of solid tumor tissues, but also closely related to tumor stage, treatment and tumor prognosis. CD73 can exert a wide range of immunosuppressive effects through multiple pathways such as A2A receptor, regulation of regulatory T cells, and inhibition of inflammation. Blocking CD73 molecules can not only effectively activate anti-tumor immune responses, but also significantly improve the clinical efficacy of programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) antibodies. Thus, CD73, as a new immunological checkpoint molecule in the tumor microenvironment, may become a promising new immunotherapy target following CTLA4, PD-1/PD-L1.