Acyl-CoA binding protein (ACBP) exhibits the activity of autophagy and lipid metabolism regulation in mammals, but its indispensable role in appetite regulation has received great attention in recent years. However, its feeding regulation function in fish is unclear. In this study, we cloned the acbp gene of Siberian Sturgeon (Abacbp) which possesses high homology with those of other vertebrate species and extremely high expression in duodenum and hypothalamus. Interestingly, Abacbp mRNA was significantly increased by short-term fasting but decreased after long-term fasting and recovered after refeeding, suggesting its latent ability in appetite regulation and compensatory growth (CG). Moreover, intraperitoneal injection of Siberian sturgeon ACBP protein (AbACBP) promoted food intake and the expressions of anorexigenic factors were down-regulated and the orexigenic factors were up-regulated. In addition, the specific receptor of ACBP regulating feeding has yet to be identified. Still, our present study found that peripheral AbACBP caused the upregulation of cb1r and the inhibition of the PI3K-AKT-mTOR-S6k signal pathway in the hypothalamus. In conclusion, the research first explored the appetite-stimulating function and mechanism of ACBP. It is of great value to construct the expression strain to produce the appetite-promoting protein ACBP in large quantities for promoting the appetite of farmed animals.