pp32 belongs to a family of leucine-rich acidic nuclear proteins, which play important roles in many cellular processes including regulation of chromatin remodeling, transcription, RNA transport, transformation and apoptosis. pp32 is described as a new tumor suppressor. It is unknown as to how pp32 works in tumor suppression. We found that overexpression of pp32 in human Jurkat T cells inhibits cell growth, and silenced pp32 promotes growth. We first showed that hyperacetylation and hyperphosphorylation of histone H3 are required for T-cell activation. Phosphorylation of histone H3 precedes acetylation during T-cell activation. pp32 specifically binds to histone H3 and blocks its acetylation and phosphorylation. pp32 directly initiates caspase activity and also promotes granzyme A-mediated caspase-independent cell death. Taken together, pp32 plays a repressive role by inhibiting transcription and triggering apoptosis.