To investigate the effects of predation by the paddle crab Charybdis japonica on the culture and survival of scallops (Mizuhopecten yessoensis) during bottom culture, we investigated the behavioral characteristics of three sizes (small, medium, and large) of scallops in response to exposure to crabs. We found that scallops escaped from crab predation by continuous shell closure or movement. Shell closure force increased with scallop size, and scallops of the same size that were stimulated by the presence of crabs closed their shell more frequently than control scallops. We also measured the activities of superoxide dismutase, catalase, arginine kinase, and octopine dehydrogenase in the gill, adductor muscle, and mantle of scallops before and after exposure to predation. Tissues that showed significant differences between control and test specimens were selected for deep sequencing of the transcriptome to identify and validate the key genes that were sensitive to predation. We found that when M. yessoensis is stimulated by the presence of predators, its behavioral characteristics and related physiological and ecological indexes undergo significant changes. The results are relevant for developing specifications for M. yessoensis seedling casting during bottom culture.