In order to improve the degradation rate of cellulose in biomass and the yield of 5-hydroxymethylfurfural (5-HMF), the process for the degradation of cotton stalk to the 5-HMF generation with hydrothermal method were studied. The influences of various factors on the degradation of cellulose and 5-HMF synthesis were analyzed to determine the optimum process operating conditions; the dynamics of 5-HMF preparation from cotton stalk with hydrothermal method with or without catalyst SO42-/ZrO2 were analyzed. The results showed that when the reaction carried out at 230 ℃ for 90 min and the dosage of catalyst SO42-/ZrO2was 20%, the degradation rate of cellulose is up to 94.43% and the yield of 5-HMF is about 25.3%, which increased by 79.4% compared with no catalyst under the same conditions. The results of kinetics study showed that catalyst SO42-/ZrO2 had positive catalytic effect on cellulose degradation and 5-HMF synthesis, and with the addition of catalyst SO42-/ZrO2, the activation energy of cellulose degradation reaction decreased from 106 kJ·mol-1 to 96.7 kJ·mol-1 and the activation energy of the preparation of 5-HMF decreased from 119.4 kJ·mol-1 to 84.2 kJ·mol-1.