Oncological diseases remain the main cause of death and disability of the population worldwide. The most malignant types of cancer include of pancreas, liver and brain tumors. Modern methods of therapy (including chemoradiation, targeted and immune therapy) do not allow achieving the desired effectiveness in this group of patients. In this regard, new approaches to the treatment of oncological diseases are needed. The aim of this review was to discuss the mechanisms of anticancer action of Strepococcus pyogenes and other streptococcal species, as well as to consider their cancer-stimulating effects and their limitations. The review considers the current state of the problem of using bacterial oncotherapy involving streptococci A group (in particular, S. pyogenes). The involvement of S. pyogenes pathogenicity factors is discussed: M-protein, exotoxins: streptolysins S, O, superantigens, arginine deiminase, etc., as well as molecular mechanisms mediated by the host immune system cells. The authors' own data show that S. pyogenes exhibits selective M-protein-mediated cytolytic activity against C6 glioma and pancreatic adenocarcinoma (Panc) tumor cells and no activity against normal fibroblasts. The data on preclinical and clinical application of the streptococcal-based medicine OK-432 for the therapy of oncological diseases are briefly summarized. Tumor-associated properties of streptococci (induction of cytokine storm, proliferation, migration and angiogenesis of vascular epithelial cells, formation of neutrophil extracellular traps in the tumor microenvironment) caused by their interaction with immune cells of the tumor-bearing organism are also discussed. Conclusion. The research data presented in this review convincingly demonstrate that S. pyogenes, with the participation of pathogenicity factors, can directly exert an antitumor effect on cancer cells. However, it should be noted the streptococcal vaccine should be used with caution, taking into account the individual characteristics of the patient's immune system, since S. pyogenes can also have effects of the opposite nature, requiring further research. © 2025 Elsevier B.V., All rights reserved.