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A 20 days feeding experiment and 15 days reversed feeding experiment were conducted to study the growth of Pampus argenteus juveniles under different feeding strategies. A total of 900 juveniles (an average ± SD, 5.88 ± 0.98 cm and 5.69 ± 0.64 g) were divided into three feeding groups and the experiments run in triplicate. Each experimental tank contained 1000 L of water and each group was fed to satiation four times a day. Three groups were constructed: group A (fed with 100% jellyfish), group B (fed with 100% Yubao 5# feed), and group C (fed with 50% jellyfish and 50% Yubao 5# mixed feed). The remaining 200 healthy individuals respectively in groups A and B were removed following the 20 days feeding experiment and subjected to 15 days of reverse feeding, resulting in group A' (fed with 100% Yubao 5# feed) and group B′ (fed with 100% jellyfish). Yubao 5# feed is 42% protein while live jellyfish larvae with a 1–2 cm umbrella diameter contain approximately 10% protein content. After 20 days, the results showed similar growth performance in terms of weight gain and specific growth rate (P > 0.05) for group A and B, indicating that the P. argenteus juveniles were able to survive on a jellyfish diet. However, the juveniles in group C showed significant (P < 0.05) weight gain and specific growth rate (8.96 ± 0.77 and 4.739 ± 0.572, respectively) over the same culture period. Serine protease (SP) was selected to study the detoxification mechanism of P. argenteus that were fed on jellyfish, and the SP enzyme activities, mRNA, and protein expression under different culture conditions were analyzed to illustrate the detoxification effect of SP protease on jellyfish toxin. The results showed that the highest SP enzyme activities occurred in the kidneys, liver, stomach, lateral capsules, caecum, and intestine (P < 0.05), with enzyme activity in the order group A > group C > group B, group A > A', and group B′ > B (P < 0.05). The highest enzyme activity of 188.91 UL /L was observed in group A when P. argenteus were fed jellyfish exclusively for 20 days (P < 0.05). The results indicate that jellyfish were the main contributors to the changes observed in the SP mRNA, protein, and enzyme activities. Our results indicate that P. argenteus juveniles can survive when feeding only on jellyfish and grow more rapidly when 50% jellyfish is added to the feed than when fed with jellyfish or Yubao 5# feed alone. SP enzymes, which are sensitive to jellyfish, play an important regulatory role in the digestion and decomposition of jellyfish by P. argenteus , and the kidneys are the most important organ for the detoxification and regulation of jellyfish toxin. • Pampus argenteus juveniles are able to maintain growth by feeding only on jellyfish. • Addition of jellyfish to feed significantly improves the growth of Pampus argenteus. • Serine protease in the kidney of Pampus argenteus plays a detoxifying role against jellyfish toxins. [ABSTRACT FROM AUTHOR]