The World Health Organization's smallpox eradication program extensively utilized the Vaccinia virus, which is today regarded as a viable vector for gene therapy due to its distinctive features. Vaccinia virus can specifically reproduce and spread effectively in cancer cells, leading to the destruction of the tumor. Furthermore, the fast generation of viral particles, the ability to infect a wide variety of hosts, the big genome size (about 200 kb), and safe handling make the vaccinia virus an appropriate choice as a vector for gene therapies. Oncolytic virotherapy (OVT) is a highly prospective modality for fighting cancer that involves the use of genetically modified viruses to reproduce specifically inside cancer cells and stimulate an immune response against the tumor. Oncolytic viruses not only destroy cancer cells but may also modify the surrounding tumor microenvironment and trigger a durable defense against the tumor. Vaccinia virus has gained attention as a promising contender because of its capacity to invade a diverse array of cancer cells. In this study, we introduce the vaccinia virus, its molecular mechanism and cell cycle, and its potential to destroy cancer cells.