Abstract: In the present work the production of xylanase by Cellulomonas fimi in submerged fermentation (SmF) using tapioca stem as a sole carbon source was enhanced by medium optimization. A Plackett-Burman based statistical screening procedure was used to identify the most significant nutrient components which influence the xylanase production. From the experiments, twelve nutrient components were screened and the results revealed that peptone, yeast extract, KH2PO4 and CaCl2.2H2O were the most significant nutrient components. Central composite design (CCD) was used to determine the optimal concentrations of these four screened nutrients components and the experimental results were fitted with a second-order polynomial model at 95% level (P < 0.05), the combined effects of these nutrients on production of xylanase was also studied. The optimum concentrations are peptone–0.957g/L, yeast extract–2.5g/L, KH2PO4–3.09g/L, and CaCl2.2H2O –0.409g/L. Under these conditions, the production of xylanase was found to be 4.12 IU/ml. The results show a close agreement between the expected and obtained activity level.