Background: A 90-day experiment was conducted to study the impact of salinity on growth and physiological response of Pangasionodon hypophthalmus fingerling at the Brackish water fish farm of Central Institute of Fisheries Education (CIFE), Kakinada Centre, Kakinada, East Godavari District, Andhra Pradesh, India. Method: The study used different salinities condition such as 0 (control), 5 (T1), 10 (T2) and 15 (T3) ppt. Fingerlings (8.47±0.46 g) were gradually acclimatized to different salinities in 1000 l fibre reinforced plastic (FRP) tanks, in triplicates and fed with a commercial feed (crude protein 30%). Result: Growth indicators such as specific growth rate (SGR), feed conversion ratio (FCR), feed efficiency ratio (FRR) and protein efficiency ratio (PER) revealed that growth and survival were negatively affected above 10 ppt salinity. Significantly higher amylase and protease activities were observed up to 10 ppt group. In contrast, significantly higher cortisol (97.71±1.94 ng/ml) and glucose (113.32±2.66 mg/dl) levels in the blood were recorded in 15 ppt group. Overall, the study proved that P. hypophthalmus can be cultured in low saline water (up to 10 ppt) without affecting its growth and physiological homeostasis.