Density-dependent mortality is an important process regulating population size in nature. Although predator encounter probability is often considered as the cause of density-dependent mortality of prey species, other factors have rarely been discussed. We hypothesized that in trophic interactions between growing predator and prey, increase in prey density can lead to an increase in their predation mortality, because it reduces prey's defensive ability by limiting growth of prey individuals. To test this hypothesis, we conducted a natural pond experiment using 28 enclosures, in which high or low prey density treatments were crossed with predator presence or absence. Results revealed that prey mortality increased in high density, but only if predators were present, suggesting that density-dependent mortality occurred via predation. Prey growth in high density was slower, resulting in small-sized individuals which were easily preyed upon. Even though higher encounter rate between predator and prey in high prey densities could also explain the observed mortality pattern, an additional experiment excluded this possibility. Therefore, predator-prey size balance can be an important factor of density-dependent mortality in nature.