Study’s Novelty/ Excerpt This study successfully optimized cellulase production by Trichoderma harzianum PK5 using the One Factor at a Time (OFAT) approach, identifying copra meal and KNO3 as the best carbon and nitrogen sources. Optimal conditions included a pH of 4.0, 125% moisture concentration, 8% inoculum size, 30°C temperature, and a 7-day incubation period, yielding a high enzyme titre of 252.54±7.73 U/gds in solid-state fermentation. These findings highlight the potential of T. harzianum PK5 as a cost-effective source of cellulases for industrial applications. Full Abstract Cellulases are considered to be among the most important enzymes in the commercial market and in various industries. Their applications are widespread, leading to increased demand and high associated costs. This necessitates the search for more cost-effective cellulases from microorganisms. Therefore, the aim of this study was to optimize cellulase production by Trichoderma harzianum PK5 using the One Factor at a Time (OFAT) approach. The effects of carbon, nitrogen, and various environmental factors were studied in both submerged and solid-state fermentation setups by adjusting one factor at a time based on the optimal conditions established from the previous condition. Copra meal and KNO3 were identified as the best complex carbon and nitrogen sources, respectively, for cellulase production by Trichoderma harzianum PK5. The optimal pH of 4.0, moisture concentration of 125% (v/w), inoculum size of 8%, temperature of 30°C, and an incubation time of 7 days were determined as the optimal conditions for cellulase production by this isolate, resulting in an enzyme titre of 252.54±7.73 U/gds in solid-state fermentation. It was found that cellulase enzyme production by the isolate was constitutive. In conclusion, cellulase production by T. harzianum PK5 was significantly optimized using the OFAT approach