We identified a small molecule, with a code name H3 (N-(4-methylphenyl)-2-{5-[(3-methylphenyl)methylidene]-4-oxo-1,3-thiazolidin-2-ylidene}acetamide), that selectively reactivated p53-Y220C, rescued its transcription activity, and inhibited tumor development in mice. The gene discussed is TP53; the disease is neoplasm.