In the warfare between herbivore and host plant, insects have evolved a variety of defensive mechanisms, including allelochemical transformation and excretion. Several studies have explored the transcriptome responses of insects after host plant shifts to understand these mechanisms. We investigated the plastic responses of Heliconius melpomene larvae feeding on a native host Passiflora menispermifolia and a less strongly defended nonhost species, Passiflora biflora. In total, 326 differentially expressed genes were identified, with a greater number upregulated on the more strongly defended native host. Functional annotation showed that detoxifying enzymes, transporters and components of peritrophic membrane were strongly represented. In total, 30 candidate detoxification genes were differentially expressed, with glutathione S-transferases (GSTs) and UDP-glucuronosyltransferases (UGTs) showing the highest proportion of differential expression, 27.3% and 17.3%, respectively. These differentially expressed detoxification genes were shown to evolve mainly under the influence of purifying selection, suggesting that protein-coding evolution has not played a major role in host adaptation. We found only one gene, GSTe3, with evidence of adaptive evolution at H40, which is around the G-site and might alter enzyme activity. Based on our transcriptome and molecular evolution analysis, we suggest that transcriptional plasticity of genes in a herbivore may play an important role in adaptation to a new host plant.