Polybrominated diphenyl ethers (PBDEs) are ubiquitously distributed persistent organic pollutants (POPs) in marine environments. Phytoplankton are the entrance of PBDEs entering to biotic environments from abiotic environments, while the responding mechanisms of phytoplankton to PBDEs have not been full established. Therefore, we chose the model diatom Thalassiosira pseudonana in this study, by integrating whole transcriptome analysis with physiological-biochemical data, to reveal the molecular responding mechanisms of T. pseudonana to the toxicity of BDE-47. Our results indicated the changes of genes expressions correlated to the physiological-biochemical changes, and there were multiple molecular mechanisms of T. pseudonana responding to the toxicity of BDE-47: Gene expressions evidence explained the suppression of light reaction and proved the occurrence of cellular oxidative stress; In the meanwhile, up-regulations of genes in pathways involving carbon metabolisms happened, including the Calvin cycle, glycolysis, TCA cycle, fatty acid synthesis, and triacylglycerol synthesis; Lastly, DNA damage was found and three outcome including DNA repair, cell cycle arrest and programmed cell death (PCD) happened, which could finally inhibit the cell division and population growth of T. pseudonana. This study presented the most complete molecular responding mechanisms of phytoplankton cells to PBDEs, and provided valuable information of various PBDEs-sensitive genes with multiple functions for further research involving organic pollutants and phytoplankton.