Abstract: Autophagy is a highly conserved catabolism process in eukaryotes, a lysosomal dependent protein degradation process. Aberrated autophagy regulation is closely related to the development of several human cancers, which can promote tumor survival as well as trigger tumor death. Concomitantly, flora disorders can also directly lead to cancer by promoting mucosal inflammation or causing systemic diseases. It plays a role in regulating the immune system's response to cancer. Multiple molecular mechanisms link dysbacteriosis with autophagy activation and influence tumor progression (pro-tumor or anti-tumor) through these pathways. The current review focuses on the critical role of autophagy in the interaction between microflora and cancer, and discusses the specific molecular mechanism of the regulation of autophagy in this complex biological process. In addition, we discussed the potential of multiple molecular drugs targeting the flora/autophagy axis for cancer treatment, reviewed clinical trials targeting autophagy or microbiome, and evaluated their therapeutic potential as anti-cancer strategies.