This study aims to determine the combined effects of hydrolysis time, temperature, pH and ratio of enzyme to substrate on the degree of hydrolysis (DH) of silver catfish frame using Response Surface Methodology. The proximate compositions of silver catfish frame and silver catfish hydrolysate powder were determined as well. The effects of independent factors were described using a three-level factors Face Centered Central Composite design. The suggested hydrolysis conditions for obtaining the optimum DH using Alcalase® were – temperature of 55oC, hydrolysis time of 163 min, pH of substrate at 9.45 and an enzyme concentration of 2.0%. The generated model showed a quadratic fit with experimental data. Proximate analyses revealed that silver catfish frame contained 25.02% protein, 68.21% fat and 7.08% ash. While silver catfish frame hydrolysate powder contained 65.05% protein, 32.92% fat and 0.86% ash. The protein recovery in silver catfish frame hydrolysate was as high as 71.6%.