To investigate which TLR4 ligand is potentially involved in the activation of the TLR4 pathway in colorectal cancers, we retrieved BGN, HSPD1, HMGB1, S100A8, S100A9, TNC, hyaluronidase (HYAL1 and HYAL2), heparan sulfate proteoglycan (SDC2 also called HSPG1, and HSPG2), hyaluronan synthase (HAS1, HAS2, and HAS3), and SFTPA1 gene expression data in healthy colon control and colon cancer from the GENT2 database. The gene discussed is HMGB1; the disease is malignant colon neoplasm.