In order to improve the liquefaction yield of Salix flour, the liquefaction process of Salix flour was optimized by response surface methodology (RMS). The mono-factorial experiment was used to preliminarily optimize the liquefaction process, and on this basis, response surface methodology was used for further optimization, obtaining the quantitative mathematical relation model between the test factors and the effects of single factors as well as the inter-factor interactions on the liquefaction rate of Salix flour. It was shown that the significant external factors affecting yield of Salix flour were liquid-solid ratio, reaction temperature, reaction time and catalyst content. The optimized Salix flour liquefaction process was: liquid-solid ratio 3.68, time 143.83 min, temperature 172.18 ℃ , catalyst content 5% , and the Salix flour liquefaction yield under this condition was 97.84% , which was close to the model predicted value. In conclusion, the liquefaction process parameters obtained by response surface methodology were reliable.