Invertebrates lack the adaptive immune system homologous to that of vertebrates, thus depend exceptionally on the innate immune system for the pathogen recognition and clearance. Phagocytes play a pivotal role in the innate immunity of invertebrates, but the molecular basis underlying their phagocytic killing is still far from well understood. In the present study, phagocytes from the Pacific oyster Crassostrea gigas were efficiently sorted based on the phagocytosis of FITC-labeled latex beads by fluorescence-activated cell sorting. The differentially expressed proteins were revealed by quantitative proteome and validated by qRT-PCR and flow cytometry.