Giant clams harbor extracellular symbiotic zooxanthellae in a tubular system that pervades mainly the fleshy and colorful outer mantle. During insolation, the symbiotic zooxanthellae conduct photosynthesis and donate photosynthates to the host clam. The host could encounter hyperoxia because photosynthesizing zooxanthellae also release O2. Hence, the host tissues, particularly the outer mantle, would need to prevent plausible oxidative damages caused by the increased production of reactive oxygen species (ROS), including superoxide radical (O •−2), during insolation. Superoxide dismutases (SODs) are enzymes which scavenge intracellular O •−2. The complete cDNA coding sequence of a Manganese SOD (MnSOD) had been cloned from the outer mantle of the fluted giant clam, Tridacna squamosa. It comprised 678 bp, encoding for a 226 amino acid polypeptide of 24.9 kDa, with a mitochondrial targeting sequence. Its host origin was confirmed through phenogramic and sequence similarity analyses. After 12 h of light exposure, the transcript level and protein abundance of MnSOD/MnSOD increased significantly in the outer mantle as compared with the control kept in darkness for 12 h, which was unrelated to circadian rhythm. In light, the outer mantle could have augmented metabolic rate with increased mitochondrial ROS production due to increases in the supply of substrates to the zooxanthellae for photosynthesis and the receipt of O2 and photosynthates from the symbionts. Therefore, the light-dependable expression of MnSOD/MnSOD in the outer mantle of T. squamosa could be an antioxidative response acquired by the host to detoxify excess mitochondrial O •−2 and prevent oxidative damage attributable to its symbiotic association with autotrophic zooxanthellae.