Pichia angusta MTCC-225, a catalase-positive yeast that utilizes methanol and lighter hydrocarbons, is the subject of this investigation. An orthogonal experimental design L 16 was used to investigate the effects of methanol, a gas mixture, zero air, temperature, agitation, and salts solution on hydrocarbon utilizing P. angusta. QUALITEK-4 Software was used for automatic design and analysis of the experimental results. Among the various parameters tested, agitation contributed the highest influence (56.5%). Zero air, methanol concentration, and gas mixture showed a moderate influence on the growth of P. angusta. Methanol concentration and gas mixture showed a 10.91 and 10.12% influence, respectively, on yeast growth. Zero air played an important role, with a 15.19% influence on the utilization of hydrocarbon.