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Emodin is a widely distributed anthraquinone derivative with a variety of biological activities, one that can be efficiently produced by marine-derived fungus <i>Aspergillus favipes</i> HN4-13. However, its relatively low fermentation yield limits further development and pharmaceutical research work. In this study, Plaekett–Burman design and central composite design were adopted to optimize the fermentation conditions of <i>A</i>. <i>favipes</i> HN4-13. Optimal fermentation conditions in a 250-mL Erlenmeyer flask with 50 mL of medium were 59.3 g/L soluble starch, 10 g/L yeast extract paste, 30 g/L seawater salt, 1.04 g/L KH₂PO₄, 0.05 g/L MgSO₄·7H₂O, 0.01 g/L FeSO₄·7H₂O, seed culture 24 h, pH 5, inoculum size 18%, culture temperature 32 °C, and shaking at 160 rpm/min for 7 days. The production of emodin could achieve 132.40 ± 3.09 mg/L, with no significant difference from the predicted value (132.47 mg/L). Furthermore, KH₂PO₄ supplementation strategy was employed to regulate the mycelial morphology, upregulate the transcriptional level of biosynthesis gene cluster, and enhance emodin production (185.56 ± 4.39 mg/L).