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Abstract: Neuropeptide Y receptor Y8 (npy8br) is a fish-specific receptor with two subtypes, npy8ar and npy8br. Changes in expression levels during physiological processes or in vivo regulation after ventricular injection suggest that npy8br plays an important role in feeding regulation; this has been found in only a few fish, at present. In order to better understand the physiological function of npy8br, especially in digestion, we used CRISPR/Cas9 technology to generate npy8br^-/- japanese medaka (Oryzias latipes). We found that the deletion of npy8br in medaka larvae affected their feeding and digestion ability, ultimately affecting their growth. Specifically, npy8br deficiency in medaka larvae resulted in decreased feed intake and decreased expression levels of orexigenic genes (npy, agrp). npy8br^-/- medaka larvae fed for 10 d (10^th day of feeding) still had incompletely digested brine shrimp (Artemia nauplii) in the digestive tract 8 h after feeding, the mRNA expression levels of digestion-related genes (amy, lpl, ctra, ctrb) were significantly decreased, and the activities of amylase, trypsin, and lipase also significantly decreased. The deletion of npy8br in medaka larvae inhibited the growth and significantly decreased the expression of growth-related genes (gh, igf1). Hematoxylin and eosin (H&E) sections of intestinal tissue showed that npy8br^-/- medaka larvae had damaged intestine, thinned intestinal wall, and shortened intestinal villi. So far, this is the first npy8br gene knockout model established in fish and the first demonstration that npy8br plays an important role in digestion.