The DNA repair protein Ku acts as a heterodimer of Ku70 and Ku80 that binds to the DNA ends, nicks, or single-to-double-strand transition. It has a crucial role for DNA double-strand-break repair. Either Ku70 or Ku80 itself may have a unique function that is independent of the other Ku subunit. In this review, the role of Ku on cell proliferation and apoptosis will be discussed. Ku acts as a regulator of transcription by interacting with the recombination signal binding protein Jkappa and the NF-kappaB p50 homodimer to up-regulate p50 expression, which may regulate the proliferation of gastric cancer cells. Both Ku70 and Ku80 expressions are mediated by constitutively activated NF-kappaB and constitutively expressed cyclooxygenase-2 in gastric cancer cells, which may be related to gastric cell proliferation and carcinogenesis. In addition, nuclear loss of Ku may underlie the mechanism of apoptosis in pancreatic acinar cells after oxidative stress.