Colorectal cancer (CRC) is one of the main reasons of tumor-related deaths worldwide. At present, the main treatment is surgery, but the results are unsatisfactory, and the prognosis is poor. The majority of patients die due to liver or lung metastasis or recurrence. In recent years, great progress has been made in the field of tumor gene therapy, providing a new treatment for combating CRC. As oncolytic viruses selectively replicate almost exclusively in the cytoplasm of tumor cells and do not require integration into the host genome, they are safer, more effective and more attractive as oncolytic agents. Newcastle disease virus (NDV) is a natural RNA oncolytic virus. After NDV selectively infects tumor cells, the immune response induced by NDV’s envelope protein and intracellular factors can effectively kill the tumor without affecting normal cells. Reverse genetic techniques make NDV a vector for gene therapy. Arming the virus by inserting various exogenous genes or using NDV in combination with immunotherapy can also improve the anti-CRC capacity of NDV, and good results have been achieved in animal models and clinical treatment trials. This article reviews the molecular biological characteristics and oncolytic mechanism of NDV and discusses and experiments on NDV anti-CRC capacity and clinical treatment. In conclusion, NDV is an excellent candidate for cancer treatment, but more preclinical studies and clinical trials are needed to ensure its safety and efficacy.