TUSC2/FUS1 is a novel tumor suppressor gene identified in the human chromosome 3p21.3 region where allele losses and genetic alterations occur early and frequently for many human cancers. Expression of TUSC2 protein is absent or reduced in the majority of lung cancers and premalignant lung lesions. Restoration of TUSC2 function in 3p21.3-deficient non-small cell lung carcinoma cells significantly inhibits tumor cell growth by induction of apoptosis and alteration of cell cycle kinetics. TUSC2 may induce apoptosis through the activation of the intrinsic mitochondrial-dependent and Apaf-1-associated pathways and inhibit the function of protein tyrosine kinases including EGFR, PDGFR, AKT, c-Abl, and c-Kit.