This study examined the expression pattern of programmed cell death 5 (PDCD5) in cochlear hair cells and spiral ganglion neurons (SGNs) and its association with age-related hearing loss in mice. Sixty C57BL/6J (C57) mice at different ages were divided into four groups (3, 6,9 or 12 months). PDCD5 expression was detected by using immunohistochemistry, real-time PCR and Western blot. Morphological change of the cochleae was also evaluated by using immunoassay. The results showed that the expression of PDCD5 had a gradual increase with ageing in both protein and RNA levels in C57 mice, as well as gradually increased apoptosis of cochlear hair cells and SGNs. In addition; we also found that caspase-3 activity was enhanced and its expression was enhanced with ageing. It is implied that overexpression of PDCD5 causes the increase in caspase-3 activity and the subsequent increase of apoptosis in cochlear hair cells and SGNs, and thereby plays a role in the pathogenesis of presbycusis. Thus, PDCD5 may be a new target site for the treatment and prevention of age-related hearing loss.