S100A8/A9 can regulate the initiation, proliferation, invasion, metastasis, angiogenesis, chemoresistance, and apoptosis of tumor cells by binding with its receptors scattered in tumor cell surface, including RAGEs, TLR4, EMMPRIN, MCAM, ALCAM, and NPTN, mostly by activating the JNK, ERK, P38 MAPK, PI3K/Akt, NF-κB, TGFβ, and STAT3 signal transduction pathways; thus, they can be potential targets for cancer treatments. The gene discussed is STAT3; the disease is cancer.