Cellulosic materials present in nature as environmental wastes and also it is considered as a source of energy and sugars. Biological degradation of cellulosic materials using cellulose-degrading enzymes can solve these issues. For economic process, cellulase productivity should be at the highest yield and lowest cost. Therefore the improvement of cellulase productivity is a crucial step for beneficial process. The recent biotechnological methods such as mutagenesis and modeling provided effective tools for stimulation of microbial enzyme production. In the current work, Gamma and UV-radiation and Ethidium bromide have been used for improving cellulase production by a promising fungal isolate. In addition, statistical methods have been used to optimize nutritional and environmental conditions. The fungal isolate have been identified on molecular basis as Aspergillus flavus and given an accession number in NCBI. Mutagenesis resulted in 343.77% increase in cellulase activity compare with the wild-type, while statistical modelling resulted in 1.48% compared with the mutated cells productivity. The over all used methods resulted in 510.69% increase in cellulase production by the mutated Aspergillus flavus compared with the wild-type. Data showed that Aspergillus flavus is a promising cellulase fungal source for application in biotechnological industries. Mutagenesis and statistical modeling provide vital tool as driving force for evolution.