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Cadmium (Cd) is a heavy metal toxicant and is widely distributed in aquatic environments. It can cause excessive production of reactive oxygen species (ROS) in the organism, which in turn leads to a series of oxidative damages. Thioredoxin (Trx), a highly conserved disulfide reductase, plays an important role in maintaining the intracellular redox homeostasis in eukaryotes and prokaryotes. <i>Phascolosoma esculenta</i> is an edible marine worm, an invertebrate that is extensively found on the mudflats of coastal China. To explore the molecular response of <i>Trx</i> in mudflat organisms under Cd stress, we identified a new <i>Trx</i> isoform (Trx-like protein 1 gene) from <i>P. esculenta</i> for the first time, designated as <i>PeTrxl</i>. Molecular and structural characterization, as well as multiple sequence and phylogenetic tree analysis, demonstrated that <i>Pe</i>Trxl belongs to the Trx superfamily. <i>PeTrxl</i> transcripts were found to be ubiquitous in all tissues, and the highest expression level occurred in the coelomic fluid. Exposure to three sublethal concentrations of Cd resulted in the upregulation and then downregulation of <i>PeTrxl</i> expression levels over time in coelomic fluid of <i>P. esculenta</i>. The significant elevation of <i>PeTrxl</i> expression after 12 and 24 h of Cd exposure at 6 and 96 mg/L, respectively, might reflect its important role in the resistance to Cd stress. Recombinant <i>Pe</i>Trxl (<i>rPe</i>Trxl) showed prominent dose-dependent insulin-reducing and ABTS free radical-scavenging abilities. After exposure to 96 mg/L Cd for 24 h, the ROS level increased significantly in the coelomic fluid, suggesting that Cd induced oxidative stress in <i>P. esculenta</i>. Furthermore, the injection of <i>rPe</i>Trxl during Cd exposure significantly reduced the ROS in the coelomic fluid. Our data suggest that <i>Pe</i>Trxl has significant antioxidant capacity and can protect <i>P. esculenta</i> from Cd-induced oxidative stress.