Phosphotungstic acid (H₃PW₁₂O₄₀, HPW), a kind of solid acid, is widely used for hydrolyzing cellulose to prepare microcrystalline cellulose (MCC). MCC is usually used in food, synthetic leather, chemical and pharmaceutical industries. The use of response surface methodology (RSM)can help avoid the random error caused by single factor experimental design, reduce test times and cost, and improve quality. The RSM was used in this study to determine the following optimal process conditions: H⁺ molar quantity, 31 mmol/L; reaction temperature, 93 ℃; reaction time, 2 h; and solid to liquid ratio, 1:38. Under these conditions, the crystallinity of MCC was 77.4%. Thus, the use of RSM allows the preparation of MCC with higher performance and increased crystallinity.