The optimization of solid-substrate medium and fermentation conditions for the production of enzyme carrageenase by a Pseudomonas aeruginosa ZSL-2 was achieved for the first time by employing an orthogonal array testing strategy (OATS). Of the four different substrates tested, wheat bran showed maximum production of carrageenase enzyme. The factors that influence the solid-substrate fermentation (SSF) conditions such as, moisture content, moistening agent, temperature, pH, inoculum size, additional carbon source and the fermentation period for the production of enzyme were studied by one-factor at a time and also by L9(34) an orthogonal array method. The maximal production of k-carragenase (7.44 U/g) dry bacterial bran was achieved at moisture level 1:2.5 (w/v; wheat bran to moisture level), moistening agent IV, inoculum size (10%), temperature 37°C and 48 h of fermentation. The effects of various parameters like medium, inoculum size, temperature, moistening agent, moisture level, incubation period, and supplementation of other carbon sources on the production of carrageenase by SSF using OATS is investigated and the results are presented and discussed.