Predation has been a major driver of the evolution of prey species, which consequently develop antipredator adaptations. However, little is known about the genetic basis underpinning the adaptation of prey to intensive predation. Here, we describe a high-quality chromosome-level genome assembly (approx. 145 Mb, scaffold N50 11.45 Mb) of Daphnia mitsukuri, a primary forage for many fish species. Transcriptional profiling of D. mitsukuri exposed to fish kairomone revealed that this cladoceran responds to predation risk through regulating activities of Wnt signalling, cuticle pattern formation, cell cycle regulation and anti-apoptosis pathways. Genes differentially expressed in response to predation risk are more likely to be members of expanded families. Our results suggest that expansions of multiple gene families associated with chemoreception and vision allow Daphnia to enhance detection of predation risk, and that expansions of those associated with detoxification and cuticle formation allow Daphnia to mount an efficient response to perceived predation risk. This study increases our understanding of the molecular basis of prey defences, being important evolutionary adaptations playing a stabilizing role in community dynamics.