Abstract: Glutathione peroxidase (GPx) is an important member of cellular enzymatic antioxidant system regulating stress response of host as an acute protein. In this study, a selenium-dependent glutathione peroxidase (TgGPx) gene from blood clam Tegillarca granosa was cloned and analyzed by rapid amplification of cDNA ends (RACE). The nucleotide sequence of TgGPx was consisted of 1195 bp with a 45 bp 5'UTR a of 511 bp 3'UTR and 639 bp open reading frame (ORF) encoding a peptide of 212 amino acids with an estimated molecular mass of 24.3 kD and a theoretical isoelectric point of 8.33. TgGPx had a characteristic codon at ²⁰²UGA²⁰⁴ that corresponded to Selenocysteine as U53. A selenocysteine insertion sequence (SECIS) element was identified in the 3'-UTR of TgGPx cDNA, which forms a stem-loop secondary structure. SECIS element plays a decisive role in the translation of the stop codon UGA into a selenocysteine. Multiple sequence alignment and phylogenetic analysis revealed that there were different types of GPx genes in mollusks. TgGPx has a closer phylogenic relationship with GPx1 and GPx2. TgGPx expressed in all five tissues with the highest mRNA level in mantle and the lowest in haemocytes. The expression pattern of TgGPx in adult may support its role in adult tissue growth and larval development. TgGPx was significantly up-regulated in hepatopancreas by heavy metals (Zn²⁺, Cu²⁺ and Cd²⁺) exposure, suggesting TgGPx may play a role in stress response and maintaining the body's normal function in T. granosa.