No previous studies have examined the effect of Hippophae rhamnoides fruit extract (HRE), which contains both water and fat soluble vitamins, on cisplatin-induced ototoxicity. Therefore, the aim of the study was to investigate the effects of FIRE on cisplatin-induced ototoxicity in Guinea pigs and to evaluate the biochemical, gene expression and histopathological changes associated with cisplatin use. Experimental animals were divided into three groups: healthy (HG), HRE+cisplatin (HRC) and cisplatin control (CCG) groups. Biochemical, gene expression and histopathological examinations were carried on the removed inner ear tissues. In the HRC group, the oxidant parameter was lower and the anti-oxidant parameter was higher than in the CCG. These results are supported by gene expression levels and histopathological results. The use of FIRE against cisplatin-induced oxidative ototoxicity may be easier, more cost effective and more beneficial than the use of vitamins alone or in combination with each other.