Background: Spirulina platensis water extract (SP) could decrease hearing degeneration via reducing oxidative stress damages in the auditory system of senescence-accelerated prone-8 (SAMP8) mice. This study aimed to investigate the effects of SP on the caspase-independent apoptosis in the cochlea and brainstem of SAMP8 mice.Methods: Twelve 11-month-old SAMP8 mice were randomly divided into two groups: control group (SAMP8 mice was fed a normal diet) and spirulina group (SAMP8 mice was fed a normal diet with oral supplementation SP for 6 weeks. Auditory brainstem responses (ABRs) were measured in the beginning and at the end of the study. Cochlear histology and immunochemistry and Western blotting of brainstem were performed at the end of the study.Results: Compared with control group, spirulina group had significantly lower ABR thresholds using click sound stimulation at the end of this study. The spirulina group had significantly higher counts of outer hair cells (OHC) and spiral ganglion neuron (SGN) density in the middle turn of the cochlea. The spirulina group had significantly lower expressions of poly (ADP-ribose) polymerase-1 (PARP-1) and apoptosis-inducing factor (AIF) in the cochlea. Also, the spirulina group had significantly lower expression of PARP-1, but not the AIF, in the brainstem.Conclusions: SP could decrease hearing degeneration in SAMP8 mice possibly via reducing caspase-independent apoptosis signal pathway in the cochlea and brainstem.