A target of NESH-SH3/Abi3bp (TARSH) was originally identified as an SH3 domain-binding molecule of the NESH-SH3/Abi3 protein that is involved in Rac-dependent actin polymerization. In recent studies, TARSH gene expression was dramatically induced in mouse embryonic fibroblasts (MEFs) replicative senescence and suppressed in human lung carcinoma specimens and thyroid carcinomas. However, the molecular mechanism underlying the regulation of TARSH in tumorigenesis remains unclear. Here, we address a p53-dependent apoptosis function of the mouse TARSH gene using RNAi-mediated suppression of endogenous TARSH expression. Our results will be useful in the discovery of a novel therapeutic target in lung carcinoma.