<p>Salinity intrusion driven by climate change is increasingly constraining freshwater availability for striped catfish (<i>Pangasianodon hypophthalmus</i>) aquaculture, raising critical concerns regarding the feasibility of grow-out production in salinity-affected regions. While the effects of salinity on early life stages of this species have been widely investigated, information on grow-out performance and product quality under elevated salinity remains limited. This study evaluated the effects of four salinity levels (0, 5, 10 and 15 psu) on growth performance, survival, feed utilization, digestive enzyme activities, physiological responses, and fillet quality of striped catfish during a 90-day grow-out period. Fish with an initial body weight of 120–140&#xa0;g were stocked at a density of 50 fish m⁻³ and gradually acclimated to the target salinities. The results showed that moderate salinities (5–10 psu) temporarily enhanced growth performance, survival, and feed conversion efficiency during the first 60&#xa0;days of culture. However, prolonged exposure resulted in reduced growth rates and salinity-dependent modulation of digestive enzyme activities. Growth impairment emerged at 10 psu after extended exposure and became more pronounced at 15 psu, accompanied by increased plasma osmolality, ion concentrations (Na⁺ and Cl⁻), cortisol, and glucose levels. Fish reared at 15 psu consistently exhibited the lowest growth performance, survival and feed efficiency throughout the experimental period. Salinity significantly affected fillet proximate composition, notably moisture, ash, and lipid contents, whereas protein content and sensory attributes were not influenced by salinity. Overall, these findings suggest that low to moderate salinities (5–10 psu) may be used as a short-term adaptive strategy, particularly within the first 60&#xa0;days of the grow-out period; however, prolonged exposure compromises growth efficiency and physiological stability, limiting their suitability for long-term production.</p>