Niclosamide is a FDA-approved anthelminthic drug for the treatment of parasitic infection. However, over the past few years, the increasing evidence has shown that Niclosamide could treat diseases beyond parasitic diseases, which include metabolic diseases, immune system diseases, bacterial and viral infections, other types of diseases and cancer. Therefore, we systematically review the pharmaceutical activities and therapeutic prospects of Niclosamide in human disease and cancer, and summarize the related molecular mechanisms and signaling pathways, which provides theoretical support for the new therapeutic value of old drug.