Colorectal cancer is the second leading cause of cancer-related death worldwide, and its occurrence and development are complicated by the dynamic regulation of autophagy: autophagy is a highly conserved self-degradation process that degrades cytoplasmic components through the lysosomal pathway. Therefore, in the occurrence and development of colorectal cancer, autophagy substantially affects the responsiveness of cancer cells to conventional therapies (chemotherapy, radiotherapy, immunotherapy) by regulating DNA damage repair, cell death pathway, cell proliferation and other key processes. Therefore, targeting autophagy pathway is likely to become a more powerful strategy to overcome drug resistance in colorectal cancer. More importantly, existing evidence suggests that autophagy plays a tumor suppressor role in the early stage of colorectal cancer, and then switches to a pro-tumor role during disease progression and drug-induced stress. Based on this, this paper systematically and rigorously summarizes the potential and advantages of autophagy inhibitors combined with conventional therapy in the treatment of colorectal cancer, and leads to its clinical application prospects, thereby providing a new perspective for optimizing the treatment of colorectal cancer.