Nucleolin is a highly conservative multifunctional protein in the cell nucleus, also called C23, which is rich expressed in the nucleolus and participates in a variety of biological process. In recent years, the role of nucleolin in the development of tumor has received extensive attention. Nucleolin regulates a variety of tumorigenic gene (such as Akt) indirectly or directly influence cell cycle to promote cell proliferation, as well as stabilizes antiapoptotic factor IL-9 and bcl-2 reduced tumor cell apoptosis, activates the related gene in autophagy pathway induced autophagy. In tumor progression, nucleolin promotes the secretion of angiogenin and activates endothelial cells (EC), meanwhile activates chemokine signaling pathways to increase tumor cell migration and invasion. Recently, in the treatment of nucleolin, aptamer, polypeptide, and immunizing agent make a progress, and as an independent prognostic marker, nucleolin is of great value. Futher exploration on the relationship between nucleolin and tumor, as well as the molecular mechanism of tumor development helps provide potential biological targets for the treatment of tumor.