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In this study, inorganic flocculant with biodegradable polymer flocculant was usedfor microalgae harvest. The aim of this study was to optimize the concentration of inorganic flocculant, the concentration of biodegradable polymer flocculant and reaction volume for decreasing the amounts of flocculant and obtaining the suitable pH range for seawater by response surface methodology. The flocculation of three marine microalgae, Chlorella ellipsoidea, Dunaliella bardawil, and Dunaliella tertiolecta, using inorganic flocculants and biodegradable polymer flocculants was investigated. The results indicated that the optimal flocculant quantity showed 0.1 g/L of ferric chloride, 7.5 g/L of chitosan on Chlorella ellipsoidea. In the case of Dunaliella bardawil, the optimal flocculant quantity showed amount of ferric sulfate more than 0.12 g/L and chitosan more than 0.75 g/L. In the case of Dunaliella tertiolecta, the optimal flocculant quantity showed 1.0 g/L of sodium aluminate, 0.75 g/L of chitosan.