Vast application spectrum of cellulases especially for bioconversion of lignocellulosics into simple sugars for production of biofuel, chemicals, and other industrial products in an environmentally benign manner, faces bottleneck due to unavailability of process‐apt cellulases, and high production cost of enzymes. Solid state fermentation (SSF) offers several advantages over submerged fermentation (SmF) including the cost‐effective production of enzymes particularly using agricultural residues as substrates. Bacillus subtilis MS 54, a recently isolated bacterium was previously shown to produce thermostable and wide range pH stable cellulase under SmF. This study reports the Design of experiments (DoE) based optimization of process variables for cellulase production from B. subtilis MS 54 under SSF. Plackett–Burman (PB) design and response surface methodology (RSM) were used, respectively, for selection of significant process variables, and for optimization of the selected variables. Three process variables, that is, moisture content, maize bran and almond shell, earmarked based on PB‐design, were optimized by RSM to achieve cellulase yield enhancement by 2.02‐fold as compared with that under unoptimized conditions. Application of maize bran and almond shells as substrates for bacterial cellulase production under SSF is being reported for the first time. Solid‐state fermentation coupled with DoE tools represents a cost‐effective strategy for production of industrial enzymes. © 2017 American Institute of Chemical Engineers Environ Prog, 36: 1123–1130, 2017