The signal pathway of apoptosis induced by nuclear DNA damage is getting explicit gradually. But the relationship between the mitochondrial DNA damage and apoptosis remains unclear. The rate of apoptosis is influenced significantly by the break, depletion and dysfunction of mitochondrial DNA. The reaction of ρ⁰ cell to several of apoptotic inducible factors is different from its parental cell lines. The generation of ROS is not the essential condition of the mitochondrial DNA damage induced apoptosis and the cascade may be initiated by mitochondrial DNA damage itself. In a word, further study will be needed to know what role does the mitochondrial DNA damage act in the signal pathway.