Resistance to conventional antitumour therapies and Hypoxia in patients with advanced solid tumours are two major reasons for the failure of conventional anti-tumour therapies. Therefore, it is important to find a new therapeutic method that can overcome these problems. An attenuated anaerobic bacterium, Clostridium novyi- NT, could target Hypoxic and Necrotic areas of tumours causing tumour lysis and stimulating a host anti-tumour immune response. To the best of our knowledge, the combination of bacterial anti-tumour therapy, chemotherapy, radiotherapy and immunotherapy may promote tumour regression, inhibit metastasis and develop a new strategy for the treatment of solid tumours. However, the possible molecular mechanisms of the combined therapies are still the biggest challenge. This review provides an overview of the history of bacterial cancer therapy and the development of a non-lethal strain of Clostridium novyi. Below is a precise definition of Hypoxic conditions in solid tumour tissue. To understand the anticancer effect of Clostridium novyi- NT spores, possible cell death mechanisms were summarised by the enzyme phospholipase C (nt01cx0979), which is secreted by Clostridium novyi- NT spores after germination in tumour tissue. The function of Clostridium novyi- NT spores in stimulating the host immune system to elicit anti-tumour responses was reviewed. Then, the results of anti-tumour combination therapies based on Clostridium novyi- NT spores were compiled. Identifying the molecular mechanisms of Clostridium novyi- NT in treating tumours and inducing cell death in invasive cancer cells, ultimately leading to tumour regression, may develop promising clinical strategies in the combined treatment of solid tumours.