Modern aquaculture requires the reduction of the feeds cost, which can partly be achieved by minimal use of dietary animal protein. Therefore, this experiment assessing the nutritional potential of using high protein distillers dried grains (HP-DDG) in formulation of affordable striped catfish, Pangasianodon hypophthalmus, diet for more sustainable development of aquaculture. Four diets containing 0, 25, 50 and 75% HP-DDG as partial replacement of fish meal were fed to P. hypophthalmus (108.58 ± 0.17 g fish−1) reared in circular fibreglass tanks (1 m3 adjusted to 0.8 m3; three replicates treatment−1) at an intial stocking density of 30 fish tank−1. The experiment lasted 14 weeks. The results indicated a significant negative linear regression of growth response (SGR and FCR) with increasing fish meal replacement with HP-DDG according to these formula Y = -0.00444*X + 0.724 and Y = 0.00952*X + 1.583, respectively. The reduction of SGR was 16.44 and 32.88%, and the increasing of FCR was 13.66 and 21.74% by 25 and 50% HP-DDG replacement, respectively compared to the control. The whole-body protein content was significantly decreased and lipids increased with the highest HP-DDG inclusion level. The plasma proteins tended to decrease with increasing HP-DDG (%). Therefore, replacing 25% of fish meal by HP-DDG is acceptable for growth and feed utilization. However, the economic revenue indicated the visibility of replacing 50% of fish meal using HP-DDG as determined by feed cost kg−1 gain (Y = 0.0396*X + 12.84) and net income (Y = -0.2908*X + 47.02).