The helical peptide KLA (KLAKLAKKLAKLAK) is a well known inducer of cellular apoptosis, acting to disrupt the mitochondrial membrane. However, its weak cellular uptake impedes developing any further applications. Here, we have utilized a novel in-tether chiral center induced helicity strategy (CIH) to develop a potent apoptosis inducer based on this KLA seqeunce. Notably, for the two resulting epimers of CIH-KLA peptide, CIH-KLA-(R) epimer exhibited superior cellular uptakes and special mitochondrial targeting when compared with its S counterpart. This work provides a promising and versatile method to modify KLA peptide and a proof-of-concept application for the CIH strategy in modifying bio-active peptides.