ZAS3 is a large zinc finger transcription repressor that binds the ${kappa}B$-motif via two signature domains of ZASN and ZASC. A loss-of-function study showed that lack of ZAS3 protein induced accelerated cell proliferation and tumorigenesis. Conversely, gain-of-function studies showed that ZAS3 repressed $NF{kappa}B$-activated transcription by competing with $NF{kappa}B$ for the ${kappa}B$-motif. Based on these observations, we hypothesize that ZAS3 promotes apoptosis by interrupting anti-apoptotic activity of $NF{kappa}B$. Here, we present evidence that upon $TNF{alpha}$ stimulation, ZAS3 inhibits $NF{kappa}B$-mediated cell survival and promotes caspase-mediated apoptosis. The inhibitory effect of ZAS3 on $NF{kappa}B$ activity is mediated by neither direct association with $NF{kappa}B$ nor disrupting nuclear localization of $NF{kappa}B$. Instead, ZAS3 repressed the expression of two key anti-apoptotic genes of $NF{kappa}B$, TRAF1 and TRAF2, thereby sensitizing cells to $TNF{alpha}$-induced cell death. Taken together, our data suggest that ZAS3 is a tumor suppressor gene and therefore serves as a novel therapeutic target for developing anti-cancer drugs.