Ammonium hexafluorosilicate and ammonium bicarbonate as raw materials were used to prepare silica and ammonium fluoride (NH4F). Based on the single factor experiment and Box-Behnken design response surface methodology, a quadratic regression model was established for variance analysis and verification. The influences of four single factors (liquid-solid ratio, ingredient ratio, reaction temperature and reaction time) on silica yield and NH4F concentration were investigated. By the response surface analysis, the better process conditions are as follows: liquid-solid ratio 8, ingredient ratio 5.49, reaction temperature 76.5 ℃, reaction time 49.08 min. Under these conditions, the verification experiment was carried out. The silica yield is 96.90%, and the NH4F concentration is 2.02 mol/L. There is no significant difference between the predicted value and the experimental value, which verifies the reliability of the quadratic regression model. XRD, IR, TG-DSC, SEM, BET characterization, particle size analysis and performance test of the product silica were carried out. The concentration of the product NH4F was measured by the fluoride ion selective electrode method, and its performance was tested. It is confirmed that the particle size of silica product is micron-sized, and silica is a mesoporous material with specific surface area of 316.83 m2/g. The mass fraction of SiO2 is as high as 97.77%, and the appearance, heating loss, ignition loss, pH value, heavy metal content, and oil absorption value all meet industry standards. The content of ammonium fluoride, free acid and fluorosilicate in NH4F product all meets the national standard of the People’s Republic of China.