Nucleolin or C23, is one of the most abundant non-ribosomal phosphoproteins of nucleolus. However, in several cancers, nucleolin is highly expressed both intracellularly and on the cell surface. So, it is considered as a potential target for the diagnosis and cancer therapy. Targeting nucleolin by compounds such as AS1411 aptamer can reduce tumor cell growth. In this regard, interest has increased in nucleolin as a molecular target for overcoming cancer therapy challenges. This review paper addressed recent progresses in nucleolin targeting by the G-rich AS1411 aptamer in the field of cancer therapy mainly over the past three years. •Nucleolin is highly expressed both intracellularly and on the cell surface.•It is considered as a potential target for the cancer diagnosis and therapy.•AS1411 a 26-mer DNA aptamer that binds nucleolin.•This review paper addressed recent progresses in nucleolin targeting by the AS1411.