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Higher quantities of arsenic (As) in Sargassum fusiforme limit its use as a food ingredient. The present study aimed to reduce As in S. fusiforme using sequential processing involving hot water, citric acid, and fermentation. The As content in S. fusiforme of 76.18 mg/kg was reduced to 30.47 mg/kg and 24.45 mg/kg using hot water and citric acid processing, respectively. However, the As content in S. fusiforme was reduced to 9.09 mg/kg by sequential processing with hot water and citric acid. Using response surface methodology, optimal processing conditions for S. fusiforme were determined to be treatment with hot water at 60 °C for 120 min followed by treatment with 0.4% citric acid. To further reduce the As content, the processed S. fusiforme was fermented by Lactobacillus rhamnosus, and the As content was further reduced to 1.64 mg/kg. In addition, the levels of organic acids and amino acids in S. fusiforme pre- and post-fermentation were significantly altered. These results indicated that the As content in S. fusiforme could be effectively reduced using the sequential processing with hot water, citric acid, and L. rhamnosus fermentation, and the organic acid and amino acid levels were significantly altered by L. rhamnosus fermentation.