Background and Objective: Present study aimed to investigate response of metallothionein (MT) in oyster Crassostrea sp. to the experimental concentrations of Hg and Cd in order to assess the possibility of MT usage as a biomarker of Hg and Cd contamination in this mollusk. Materials and Methods: Oysters were collected from docks of Imam Khomeini Port. After seven days acclimation period in laboratory, they were exposed with Hg at concentrations of 15 and 75 µg.L^-1 and Cd at concentrations of 15 and 150 µg.L^-1 for 14 days. MT levels were measured through spectrophotometric method after extraction and precipitation. After preparation and acid digestion, the concentration of heavy metals was quantified by atomic absorption. Results: The amounts of MT in oysters exposed with Hg and Cd were significantly increased compared with control samples (P<0.05). The highest value of MT biosynthesis in oysters exposed with concentrations of Hg and Cd were 137.2±7.6 and 312.4±17.9 µg.g^-1 w.w respectively. Exposing the oysters with Cd induced biosynthesis of MT more than three times compared with control samples. Among Hg and Cd, there was only significant correlation between biosynthesis of MT and Cd bioaccumulation in oysters (P<0.01). Conclusion: MT protein in oyster Crassostrea sp. can be considered as a suitable biomarker of Cd contamination in body and environment. Hence, it could be used for assessing and monitoring ecosystems.