The screening of the process parameters on the enzymatic hydrolysis of a blend of two lignocellulosic materials - corn cob (CC) and deseeded fluted pumpkin fruit (DFPF) using Trichoderma reesei was the focus of the present study. Four process parameters – time, temperature, substrate blend ratio and pH were screened for statistical significance using a 4 x 4 matrix of Graeco-Latin square design of experiment. The reducing sugar yield was determined using the dinitrosalisylic acid (DNS) method and maximum reducing sugar yield of 57.92mg/ml obtained in 2days at 40oC, blend ratio of 0.2:0.8 (CC:DFPF) and pH 5.5. Result of the Analysis of Variance (ANOVA) obtained showed that with 3 degrees of freedom and 6 residual degree of freedom at 95% confidence level (i.e. 0.05 significance), time, temperature and substrate blend ratio significantly affected the enzymatic hydrolysis process whereas the effect of pH was not significant. However, only time was significant at 99% confidence level (0.01 significance) while temperature, substrate blend ratio and pH were not significant. This study has highlighted the significant factors among the process variables in emzymatic hydrolysis of a blend of CC and DFPF.