To investigate the protective effect of Radix et Caulis Acanthopanacis Senticosi on cisplatin-induced ototoxicity in mice and the regulation of p38MAPK signaling pathway.Methods:According to body mass stratification，BALB/c mice were divided into a blank group，a model group and an experimental group，with 15 mice in each group.In addition to the blank group，all the mice in the other groups were intraperitoneally injected with DDP 4 mg/kg，while the experimental group was given the same amount of saline in advance by intraabdominal injection of Radix et Caulis Acanthopanacis Senticosi 4 mL/kg.The indexes were detected and evaluated after 5 days of intervention in each group.The threshold of auditory brainstem response(ABR)and apoptosis of cochlear tissue cells were detected.The expression of p38MAPK signal pathway-related protein in cochlear tissue cells was detected by Western blot.Results:Compared with the blank group，the ABR threshold shift in the model group increased at 8 Hz，12 Hz and 24 Hz(P<0.05)，and compared with model group，ABR threshold in the experimental group decreased(P<0.05).The AI of spiral ganglion cells in the blank group，the model group and the experimental group were（2.33±0.54），（19.76±0.84），（6.97±0.77），respectively.WB detection showed that the relative expression of p-p38MAPK protein in spiral ganglion cells in the blank group，the model group and the experimental group were（0.22±0.03），（0.93±0.02），（0.64±0.04），and the relative expression of p-CREB protein was（0.19±0.04），（0.84±0.05），（0.43±0.02），respectively.Compared with the model group，the expression levels of AI and p-p38MAPK，p-CREB in the spiral ganglion of the blank group and the experimental group were significantly different(P<0.05).Conclusion:Radix et Caulis Acanthopanacis Senticosi has protective effect on cisplatin-induced ototoxicity in mice.Its mechanism is related to regulating the expression of p38MAPK signaling pathway and inhibiting the apoptotic process of cochlear cells.