The aim of the present study was to investigate the influence of supplementation of lysozyme (LZM) into diet on the growth performance, muscle quality, immunity, intestinal microbiota in large yellow croaker (Larimichthys crocea) with initial body weight of 194.5 ± 0.27 g. After a 70-day feeding trial, 6 experimental diets with LZM supplementation at 0 (LZM0), 10 (LZM10), 30 (LZM30), 50 (LZM50), 70 (LZM70) and 90 mg/kg (LZM90) were tested. Results showed that the fish in the LZM70 group exhibited the lowest feed conversion ratio and the highest weight gain (WG), along with the highest trypsin and Na+/K+ ATPase activities in intestine (P < 0.05). The LZM activity in serum and intestine was significantly reduced in all dietary LZM supplemented groups compared to the LZM0 group (P < 0.05). Compared with that in the LZM0 group, the gene expressions of claudin 11, bcl-2, nlrp 3, tnf α, il-10 and tgf β in intestine in the LZM90 group were significantly elevated, while bax and caspase3 were significantly downregulated (P < 0.05). Meanwhile, the group supplemented with 90 mg/kg of dietary LZM also increased muscle crude lipid content, springiness and drip loss, along with decreased crude protein content, shear force and hardness compared with other groups (P < 0.05). Furthermore, the results of intestinal microbiota showed that compared to those in the LZM0 group, relative abundances of Fusobacterium in the LZM30 and LZM90 groups were decreased, and the relative abundances of Achromobacter, Mycoplasma and Cetobacterium were increased. In conclusion, appropriate supplementation of LZM in diet promoted the growth performance, improved immunity, adjusted intestinal microbiota and muscle quality of large yellow croaker. Furthermore, the optimal level of dietary LZM supplementation for large yellow croaker was estimated to be 67.14 mg/kg based on the quadratic regression for WG.