<p>Cancer is a leading cause of mortality. With the changes in people’s daily lifestyle and environmental pollution, the incidence of cancer has been increasing all over the world. Cancer not only increases patients’ physical and mental burdens, but also brings a huge economic burden to the society. Thus, it is urgent to develop anti-cancer therapies with low side effects and high efficiency. Nowadays, probiotics have been considered as an effective strategy owing to their anti-tumor efficacy. In this review, we comprehensively summarize anti-cancer mechanisms of probiotics. Mechanistically, cell and animal experiments have revealed that probiotics prevent and/or alleviate cancer by blocking carcinogenesis-associated signaling pathways, initiating cancer cell apoptosis, detoxifying or reducing pro-carcinogenic compounds, regulating intestinal microbiota and their metabolites, increasing the efficacy of anti-cancer therapies, inhibiting inflammation, enhancing anti-tumor immunity, and reprogramming metabolism. Clinical evidence of probiotics in cancer treatment is also summarized. Finally, it discusses the future perspectives in the safety concerns, limitation use, and strain-specific effects of probiotics.</p>