The major thrusts are: (i) firstly, and most importantly, an update on HMGB1-driven pro-inflammatory mechanisms, particularly those involving interactions of HMGB1 with Toll-like receptor (TLR) 4 and the receptor for advanced glycation end products (RAGE) that promote immunosuppression and tumorigenesis in various types of cancer; and (ii) determination of the prognostic potential of in situ and systemic measurement of HMGB1 in various types of cancer. Here, HMGB1 is linked to cancer.