Scolopendra subspinipes mutilans L. Koch has been used for cancer treatment in traditional Chinese medicine for hundreds of years. In this study, the effects of a polysaccharide-protein complex from Scolopendra subspinipes mutilans L. Koch (SPPC) on the tumor growth and immune function were assessed in sarcoma S180 and hepatoma H22 bearing mice. Results showed that SPPC significantly inhibited the growth of S180 transplanted in mice and prolonged the survival time of H22- bearing mice. In S180-bearing mice, it promoted specific and nonspecific immune response as evidenced by enhancing the activities of natural killer (NK) cells, cytotoxic T lymphocytes (CTL) and the ratio of Th1/Th2 cytokines, and increasing the percentages of CD4(+) T cells, B cells and NK cells. Furthermore, SPPC not only significantly inhibited mRNA expression and production of the immunosuppressive cytokines (IL-10 and TGF-β), but also diminished arachidonic acid (AA)-metabolizing enzymes (COX-2 and CYP4A) and their products (PGE(2) and 20-HETE) in tumor-associated macrophages (TAMs). Taken together, our results indicate that SPPC inhibits tumor growth in vivo by improving antitumor immune responses at least partly via downregulating AA-metabolic pathways in TAMs, and could act as an anti-tumor agent with immunomodulatory activity.