Temperature and salinity are among the most important factors affecting food-intake, metabolism, and growth of aquatic animals through their neuroendocrine systems. However, how the regulation of feeding, metabolism and growth are integrated under thermo-saline interaction is still unclear. In this study, modulated transcriptomic responses to temperature and salinity changes were investigated in Chinese sea bass (Lateolabrax maculatus), the economically important fish in East Asia that can adapt to diverse thermo-saline environments. L. maculatus were acclimated at different temperatures (14 °C, 21 °C, 28 °C) and salinities (freshwater and seawater) for 30 days, and their growth rate was better at 21 °C than 14 °C/28 °C (2.76-3.22 times), with mild difference between seawater and freshwater. An interaction between temperature and salinity on L. maculatus growth was detected, and low salinity (0 ppt) may mitigate the temperature (28 °C) effect. Weighted gene co-expression network analysis for L. maculatus brain transcriptomes identified growth-related temperature-salinity responsive modules, revealing the neuroendocrine gene cascade for stress-feeding-growth functions in L. maculatus. Specifically, stress-induced heat shock proteins (hspe1 and hsp30l) may stimulate the hypothalamic-pituitary-interrenal (HPI) axis (crhb and pomc), further activate anorexic genes (cart and prlh) and growth inhibiting somatostatin (sst), which was further verified through both in vitro brain culture and individual feeding test. These results revealed modulated regulation of the stress-feeding-growth cascade in L. maculatus under thermo-saline changes, which may regulate feeding behavior and ultimately control growth. These findings may provide vital guidance for the development of fast-growing L. maculatus in diverse thermo-saline environments like seawater cages, freshwater ponds, or even alkaline waters.