Increased levels of thioredoxin (Trx) occur in a number of human cancers, which may contribute to the resistance of cancers to therapy by scavenging reactive oxygen species (ROS) which are generated by various anti-cancer agents. Many human cancers have low levels of thioredoxin-binding protein (TBP-2). TBP-2 binds to Trx and blocks its reducing activity. Histone deacetylase inhibitors (HDACi) up-regulate TBP-2 in various transformed cells, associated with a decrease in Trx levels. Up-regulation of TBP-2 and decrease of Trx may contribute to the sensitivity of many hematologic and solid tumors to anti-cancer activity of HDACi.