Nucleolin (NCL) has a functional role in cancer regulation. Targeting surface NCL impaired the progression of several cancer cell types in vitro and in vivo. The present up‑to‑date review provides data to support the notion of targeting NCL among the developing anticancer approaches, including the use of anti‑NCL peptides, aptamers, anti‑NCL antibodies/pseudopeptides and NCL‑specific T‑cells. The NCL‑specific T‑cells generated by antigen presenting cells or NCL peptides illustrate the use of the platforms that open a window for using immunotherapy targeted at NCL as another very promising approach in NCL‑positive cancers.