Inhibitors of Late SV-40 Factor (LSF) are used to treat cancers such as hepatocellular carcinoma (HCC). In particular, small molecule chemical LSF inhibitors are employed. In addition, the activity and/or pattern of expression of LSF may is used to diagnose cancer, to characterize the cancer (e.g. stage, grade, prognosis, etc.) and also to develop suitable protocols for cancer treatment.