LDOC1 was isolated as a gene encoding a leucine-zipper protein whose expression was decreased in pancreatic and gastric cancer cell lines in 1999. Here, we found that overexpression of LDOC1 caused externalization of the cell membrane phosphatidylserine, which was characteristic for early-phase apoptotic events, and reduced cell viability in some human cell lines. The apoptotic process was triggered by a loss of the mitochondrial membrane potential, leading to both caspase-3-dependent and -independent pathways. Furthermore, a transcription factor, MZF-1, was revealed to interact with LDOC1 and enhance the activity of LDOC1 for inducing apoptosis.