Abstract: Oncolytic viruses are a class of natural or genetically engineered viruses that selectively infect and kill tumors, without affecting normal cells. As a new class of immunotherapy, oncolytic viruses have proved to be able to activate anti-tumor immune response, regulate tumor microenvironment, and enhance the efficacy of immune checkpoint inhibitors. However, oncolytic virus therapy still faces challenges such as mode of administration, antiviral immune response, and selection of suitable patients. This article summarizes the characteristics of oncolytic virus vectors, anti-tumor mechanisms and modification strategies of oncolytic viruses, and reviews the various combination therapies based on oncolytic viruses as well as the challenges facing oncolytic virotherapy.