Hydrodynamic cavitation (HC), which is a highly destructive force, was employed for pretreatment of sugarcane bagasse (SCB). The efficacy of HC was studied using response surface methodology (RSM) with determining parameters variedinlet pressure of 1–3 bar, temperature of 40–70 °C, and alkaline concentration of 0.1–0.3 M. At the best condition (3 bar, 70 °C and 0.3 M NaOH), 93.05% and 94.45% of hydrolysis yield of cellulose and hemicellulose, respectively, were obtained within 30 min of pretreatment time. Also, pretreatment time higher than 10 min had little to do regarding to SCB composition changes using different orifice plates (16 and 27 holes, with corresponding cavitation number of 0.017 and 0.048, respectively), with higher hydrolysis yield observed at 20 min of process. Therefore, HC-based approach could lead to a high yield of hydrolysis, as long as a treatment condition was right; it could be so at mild conditions and at short running time.