Ladybird beetles (Coleoptera, Coccinellidae) are highly diverse in feeding habits. Most of them are specialist feeders, while some can have a broad spectrum of prey. As a represented group of generalists, the tribe Coccinellini includes many aphidophagous species, but they also feed on other hemipterous insects including coccids, psyllids and whiteflies. As a result, several species are effective biological control agents or invasive species with serious non-target effect. Despite their economic importance, relatively little is known about how they adapt to new prey. In this study, comparisons of life history traits and transcriptome when ladybirds were fed by initial (aphids) and alternative prey (mealybugs) were performed in three Coccinellini species. We found that the use of alternative prey caused great decrease of performance, implied by the significant prolong of development time and decrease of survival rate and adult weight. Adaptation resulted in a set of differentially expressed genes coding chemoreceptor proteins, digestive and detoxifying enzymes. Our results suggest that these generalists do not perform well to use the alternative prey as the sole nutrition source. Although their capacity of predation might have created an opportunity to use varied prey, they have to adapt to physiological obstacles including chemoreception, digestion and detoxification in prey shift. These findings challenge the effect of Coccinellini predators on biological control of non-aphid pests, and also suggest the possibility of non-target attack of so-call specialists.