Objective To provide an overview of the main anti-tumor mechanisms of attenuated Salmonella typhimurium（ST） and explore potential reasons for the limited clinical application of attenuated ST. Methods The literatures related to clinical and basic research on attenuated ST tumor treatment and virulence at home and abroad in recent years were reviewed and the relevant mechanisms of attenuated ST tumor treatment were summarized. And then, analyses were made regarding the failure of clinical application experiments of attenuated ST based on the characteristics of attenuated ST and the human immune microenvironment. Results Attenuated ST could inhibit the growth of primary tumors and reduce the metastasis of secondary tumor due to its effect of tumor-targeting, its property of facultative anaerobic and its characteristic of being able to carry plasmids. On the other hand, the toxicity of wild strains to hosts had been reduced through biotechnology. In terms of clinical application, the anti-tumor effect of attenuated ST was far lower than expected due to excessive detoxification of ST, the elimination effect of foreign substances by the human immune system, and the inactivation effect of various proteases in the body. Conclusion As an emerging bacterial mediated anti-tumor therapy, attenuated ST will provide a new treatment option for precise treatment of cancer patients once its clinical application problems are solved.