Arthrospira, a genus of blue-green cyanobacteria, is known for its great biological activity due to the presence of a large number of substances that are potentially active against tumor cells. This review aimed to evaluate the potential of Arthrospira spp. for the treatment or reduction of several types of cancer, in addition to elucidating the mechanism of action by which their compounds act on tumor cells. A systematic review was carried out in PubMed, Science Direct, LILACS, and SciELO databases, including original studies from 2009 to 2020. A total of 1306 articles were independently assessed according to the eligibility criteria, of which 20 articles were selected and assessed for the risk of bias using seven criteria developed by the authors. Arthrospira spp. of cyanobacteria have been evaluated against eight different types of cancer, mainly colon cancer. Among all the compounds, phycocyanin was the most used, followed by peptides and photosensitizers. In general, compounds from Arthrospira spp. act as anticancer agents by inhibiting the proliferation of tumor cells, triggering cell cycle arrest, and inducing apoptosis via different signaling pathways. In addition, these compounds also exhibited antioxidant, antiangiogenic, and antimetastatic activities. Phycocyanin demonstrated better efficacy against several types of cancer via different activities and therapeutic targets. Furthermore, it was the only molecule that functioned in synergy with other drugs that are already well established for the treatment of cancer.