Response surface methodology (RSM) was employed to evaluate the optimum biodegradation of pelt skin wastes (BPSW). The parameters investigated include the pH, temperature, and enzymes mixture ratio of hydrolases, proteases and oxide - reductases on biodegradation degree for Pelt skin waste. The pH varied between 4.00 � 0.2 and 7.00� 0.2 and temperature between 30-50�C. Was used three mixtures tested having the following composition expressed as ratio between E1:E2:E3. M1- (1:1:1); M2-(2:1:1) and M3-(3:1:1) expressed in mg/L. Response surface methodology (RSM) was used to evaluate the influence of each independent variable on the overall biodegradation efficiency of waste skin. Optimum biodegradation efficiency was achieved at pH=8.4, E1 concentration in the enzyme mixture 2 mg/L and temperature 42.4 0C. Biodegradation degree is 0.996. Very similar results could be obtained for optimal extraction conditions using the desirability profiles available also in STATISTICA software.