Objective: The objective was to study the synergistic and attenuating effects of CII-3 combined with cisplatin. Materials and Methods: A Lewis tumor-bearing mouse model was established. After 15 days of continuous administration of CII-3 and cisplatin, the pathological changes in the tumor, liver, lung, and femur tissues were observed; the life prolongation rate, tumor inhibition rate, Q value, organ indices, spleen T- and B-lymphocyte proliferation activities, NK cell killing activity, the bone marrow cell proliferation rate and cell cycle phase, and the number of peripheral blood cells and bone marrow nucleated cells were measured. The expression of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in mouse serum and bone marrow tissue was measured. Results: The combination of CII-3 and cisplatin could enhance the ability of cisplatin to inhibit tumor cell proliferation and protects the liver damage and femoral injury and could significantly increase the life prolongation rate; tumor inhibition rate of cisplatin; the liver, spleen, lung, and thymus indices; the T- and B-lymphocyte proliferation activity; the NK cell killing activity; and the number of peripheral blood cells and bone marrow nucleated cells. The combination of drugs can stimulate the transformation of bone marrow cells from S phase to G2/M phase, significantly increase the proliferation rate of bone marrow cells and the contents of G-CSF and GM-CSF in mouse serum, and downregulate the mRNA and protein levels of them in bone marrow tissue. Conclusion: These results suggest that CII-3 combined with cisplatin can significantly enhance the antitumor effect and reduce the toxicity and side effects of cisplatin in Lewis tumor-bearing mice.