In this paper, we report the bioaccumulation and transformation of cadmium (Cd) by Phaeodactylum tricornutum in the presence of ethylenediamine tetra acetic acid (EDTA) and cysteine (Cys). Both EDTA and Cys can alleviate the toxicity of Cd to P. tricornutum. Short term intracellular uptake and extracellular adsorption experiments using ICP-MS indicated that the amounts of Cd accumulated on the cell surface of P. tricornutum and inside the cell decreased along with the increase of EDTA concentration, which conformed to the prediction of the Free Ion Activity Model (FIAM). However, extracellular adsorption of Cd increased at first and then decreased along with the increase in the concentration of Cys, while intracellular uptake increased under Cys concentrations from the blank value to 4.45 A mu mol/L, and then tended to remain at the same level when the Cys concentration was greater than 4.45 A mu mol/L, and this deviated remarkably from the FIAM. The interactions of Cd with-Si-OH, -C-OH and NH2(CO)-OH on the cell wall were confirmed using FT-IR and XPS studies. The results obtained using HPLC of the phytochelatins (PCs) produced by P. tricornutum under CdCl2, Cd-EDTA and Cd-Cys stress suggested that the main reason for the different effects of EDTA and Cys on the bioaccumulation and transformation of Cd by P. tricornutum was that Cys is not only a complexing ligand to Cd, as is EDTA, but also it is a precursor of the intracellular synthesizing PCs participating in the cellular defense mechanism against Cd. Furthermore, the discovery of in vivo PCs and oxidized-PCs as well as Cd-PC2 in P. tricornutum using ESI-IT-MS provided the evidence for deactivation of Cd by the PCs, reducing Cd-toxicity to P. tricornutum.National Natural Science Foundation of China [20535020, 20775062]; National 863 Hi-Tech Project of China [2006AA06Z404]; National Basic Research Program [2009CB421605