In this study, fucoidan was extracted from the Vietnamese brown seaweed Sargassum mcclurei by ultrasound -assisted extraction method (UAE) using ethanol as a solvent. The effects of single factors on total polysaccharide (TPS) content were then investigated, followed by the screening of main factors affecting TPS content based on their effect sizes and p-values in analysis of variance. The response surface methodology using the Box-Behnken design was applied to investigate simultaneous effects of four main factors including solvent-tomaterial ratio, extraction time, ultrasonic power, and extraction temperature. The optimal conditions for fucoidan extraction were identified with solvent-to-material ratio of 24 : 1 mL/g, extraction time of 49 min, ultrasonic power of 360 W, and extraction temperature of 54 � C. The highest yield of TPS obtained under these conditions was 7.1203 mg/g. Besides, extraction of fucoidan using hot water method was also carried out to compare with UAE method in terms of TPS content. The bioactivity tests showed the extract had the anti-oxidation activity with the half-maximal inhibitory concentration (IC 50 ) value of 0.4261 � 0.0008 mg/mL, cytotoxic effect on breast carcinoma cells and human lung carcinoma with IC 50 values of 95.80 � 4.75 and 129.00 � 0.66 μg/mL, respectively.