Colorectal cancer is the third most common cancer and the second leading cause of cancer death. Treatment options for advanced colorectal cancer are limited, but cytokine-induced killer (CIK) cell therapy may be a useful approach. In this type of immunotherapy, blood cells from a patient are incubated with several proteins (anti-CD3 antibodies, IL-2, and IFN-γ). This generates CIK cells, which are then injected or transfused into the patient for treatment. These cells can proliferate more quickly and exert better antitumor effects than other types of cancer-fighting immune cells. CIK cells’ killing effects are mediated primarily by binding of the membrane protein NKG2D to corresponding ligands on tumor cells and by signaling through the AMPK/Akt/mTOR, Notch, Wnt/β-Catenin, and HIF-1α pathways. Clinical studies have indicated that CIK cell treatment is generally a safe addition to routine radio- and chemotherapy and that it can help prolong survival in some patients. Notably, the CIK cell administration protocol needs to be optimized, and the mechanisms need to be further clarified. Nevertheless, the existing evidence suggests that CIK cell immunotherapy might be a helpful tool to improve treatment options for patients with colorectal cancer.