Effects of different operating factors including superficial air velocity (SAV), hydraulic residence time (HRT), protein concentration, and foam overflow height on protein removal by a foam fractionator in simulated seawater aquaculture system were investigated. This experiment was conducted on batch and consecutive modes at different combinations of the affecting factors. The foam fractionator had a diameter of 20cm and a height of 120cm and the experiment was conducted with synthetic wastewater. In 5 consecutive trials, protein concentrations in culture tank water decreased faster when the foam fractionator was operated at higher SAVs and lower HRTs. In batch trials, protein removal rates increased with an increase in SAV but decreased with an increase in URT. Higher protein concentrations in the bulk solution resulted in higher protein removal rates. Protein concentrations in the collected foam condensates increased but the foam overflow rates decreased with the increase of foam overflow heights. The results of this experiment indicate that foam fractionation would be an effective way for protein removal in seawater aquaculture systems and the performance of the foam fractionator depends largely on the operating parameters, especially SAV.