Tbx3 is a transcriptional repressor that is important for embryonic development. Overexpression of Tbx3 was found in a large variety of cancers, including breast cancer, ovary cancer, cervical cancer, lung cancer, bladder cancer and liver cancer. Tbx3 promote carcinogenesis by bypass cellular senescence via suppression of p14 ARF . Our resent studies revealed that two key motifs composed of 7 + 3 residues are essential for its transcriptional repression. Based on this finding, we designed a set of peptides to block its transcriptional repression activity and tested their antiviral effects. We found that TAT-tagged peptides (TAPs) effectively transduced hepatoma HepG2 and BEL7404 cells at almost 100% efficiency and inhibited cell growth in a dose dependent manner. Further studies revealed that the TAP treated cells underwent up-regulate apoptosis via suppression of p14 ARF both at mRNA and protein levels, demonstrating the potential of novel TAPs for anti-HCC treatment in the future.