Heavy metal pollution in food is one of the major problems affecting food safety. Cadmium is a kind of heavy metal that is non-essential, highly toxic, and easily accumulated. It enters the food chain and poisons animals and humans. Shellfish easily accumulate heavy metals because of their low metabolic rate. Scallops can accumulate high amounts of cadmium, especially compared to other shellfish, and the content of cadmium in the edible part of scallops was several times higher than that considered the national standard; hence, this has become the focus of attention. In order to understand the molecular mechanisms of high accumulation of cadmium, this study was designed to obtain transcript sequence data and assess gene expression in the digestive gland of the scallop exposed to cadmium by using molecular technology. In all, 105071 unigenes were obtained with an average size of 829 bp and a N50 length of 1573 bp. All the predicted protein sequences (unigene sequences were translated using the Transeq program of the EMBOSS suite) were searched against the NR and Swiss-Prot protein sequence databases for gene annotation. Further, 24493 unigenes were assigned to at least one GO term under one of the three categories:biological process, cellular component, and molecular function. A total of 12028 unigenes were classified functionally into 26 KOG families, including biochemical metabolism, signal transduction mechanism, defense system, cellular structure, and gene expression. Moreover, 7849 unigenes were assigned to different KEGG pathways. The most represented pathways were signal transduction (1349 members), carbohydrate metabolism (751 members), and transport and catabolism (563 members). Most of them were involved in biological progress, e.g., ATP-binding cassette transporters, oxidative phosphorylation, ribosome biogenesis in eukaryotes, MAPK signaling pathway, glutathione metabolism, serine and threonine metabolism, and steroid hormone biosynthesis. These data would provide potential molecular targets in bivalves exposed to marine pollutants for functional studies of genes and to better understand the molecular mechanisms involved in metabolic and immune pathways.