Intestinal flora form a specialized immune microenvironment that affects the occurrence and development of colorectal cancer through immunoregulation. Here, we review the research progress of intestinal flora in immune regulation therapy for colorectal cancer and summarize the relationship between intestinal flora and host or tumor immunity. Moreover, we analyzed the result of related animal experiments and clinical trials and introduce the mechanism and strategy of combination therapy based on intestinal flora immunomodulation for the treatment of colorectal cancer. Thus, this review may provide a reference for the treatment of colorectal cancer.