High mobility group box proteins are non-histon nuclear proteins which have many different functions in the cell. High mobility group box 1 is the most important member of this family. Its overexpression is showed that many cancer types such as hepatocellular carcinoma, squamous cell skin cancer, prostate cancer, gastrointestinal cancer, breast cancer, acute myeloid leukemia. Many studies suggest that HMGB1 may have an important role in the development of cancer. Therefore, HMGB1 and it's receptor RAGE is becoming an important therapeutic target. In this review, HMGB1 targeted therapies are discussed because it is a new therapeutic target in cancer.