This study attempted to optimize the microfiltration (MF) operation in the treatment of the seawater suffering from the red-tide contamination. The hollow-fiber polysulfone MF with the pore size of 2 similar to 3 mu m was used for the study. Prorocentrum micans and Thalassiosira sp. were selected in this study as the red-tide causing microbes. This study found that the cross-flow operation enabled the operation of the MF system at a higher flux than the dead-end operation. The flux was doubled for this specific seawater. The red-tide causing microbes caused the membrane fouling. The fouling extent increased with increasing cell concentration. The relationship between the pressure rate and the cell concentration was proposed depending upon the microbial species and the operation mode so that the pressure rate could be predicted when the red-tide occurred. The MF system did not experience any fouling up to the concentration of 1000 similar to 2000/mL for Prorocentrum micans. The system handled thalassiosira sp. more effectively. The system did not experience the pressure increase up to the concentration of 5000 similar to 6000/mL for Thalassiosira sp. However, as the microbial concentration increased further, the membrane fouling shortened the operation duration. When the microbial concentration reached the level of the red-tide alert activation (30,000/mL for dinoflagellate and 50,000/mL for diatom), the operation duration was significantly reduced (112 similar to 166 h). The microbial species affected the fouling. Prorocentrum micans (dinoflagellate) caused the more fouling than Thalassiosira sp. (diatom) due to SNIP (soluble metabolism product). Prorocentrum micans excreted the more SNIP, which then led to the more fouling. The chlorine addition effectively reduced the membrane fouling. The chlorine addition at 2.0 mg/L extended the operation duration by about twice. The addition of acid was also helpful in the fouling reduction. The pH adjustment to 6.5 similar to 7.0 could reduce the chlorine dosage by half.