Hyenas (family Hyaenidae) occupy a variety of different niches, of which the striped hyena () scavenges mainly on the carcasses of animals. We compared its genome with the genomes of nine other mammals, focusing on similarities and differences in chemoreception, detoxification, digestive, and immune systems. The results showed that the striped hyena's immune and digestive system-related gene families have significantly expanded, which was likely to be an adaptive response to its scavenging lifestyle. In addition, 88 and 26 positive selected genes (PSGs) were identified in the immune system and digestive system, respectively, which may be the molecular basis for immune defense system to effectively resist pathogen invasion. Functional enrichment analysis of PSGs revealed that most of them were involved in the immune regulation process. Among them, eight specific missense mutations were found in two PSGs (class II antigenandclass II antigen), suggesting important reorganization of the immune system in the striped hyena. Moreover, we identified one cathelicidin gene and four defensin genes in the striped hyenas by genome mining, which have high-efficiency and broad-spectrum antimicrobial activity. Of particular interest, a striped hyena-specific missense mutation was found in the cathelicidin gene. PolyPhen-2 classified the missense mutation as a harmful mutation, which may have aided in immune adaptation to carrion feeding. Our genomic analyses on the striped hyena provided insights into its success in the adaptation to the scavenging lifestyle.