In this study, we fed yellow drum juveniles (initial body weigh 5.57 ± 0.03 g) a fish-oil-based, soybean-oil-based (SO), or berberine chloride (BBR 50 mg kg-1 in a SO-based diet) diet with three replicates of each treatment for 56 days. Dietary BBR supplementation significantly increased growth performance but decreased SO-induced viscerosomatic index and condition factor increases. Hepatic tissue Oil Red O staining indicated that BBR supplementation completely compensated for the SO-induced excessive lipid deposition. BBR supplementation resulted in a significant decrease in saturated fatty acids but a significant increase in the proportion of n-6 polyunsaturated fatty acids in hepatic tissue. RNA sequencing revealed that amelioration of hepatic lipid deposition by BBR supplementation could be attributed to an increase in fatty acid β-oxidation. Dietary BBR also decreased the SO-induced proinflammatory gene expression, characterized by the suppression of cytokine–cytokine receptor interaction pathway. Collectively, our findings demonstrated the beneficial effects of dietary BBR on growth performance, hepatic lipid deposition, and proinflammatory gene expression. The amelioration of hepatic lipid deposition by BBR is likely caused by an increase in fatty acid β-oxidation, which promotes energy production for body growth.