To effectively solve the optimization problem of the mix design for fly ash-based polymer grouting material (FGGM), the response surface methodology was used to design the FGGM system. The effects of slag content A, sodium silicate concentration B and water-to-binder ratio C and their interaction effects on the fluidity and 28 d compressive strength of FGGM were investigated by creating quadratic polynomial prediction model and variance analysis. The results show that the ratio has the most significant effect on the fluidity of FGGM, followed by sodium silicate concentration and slag content, while slag content shows the most notable influence on the 28 d compressive strength, followed by w/b ratio and sodium silicate concentration. The results of RSM analysis indicates that, with the optimal mix proportion of A=28.8%, B=1.37 mol/kg, and water-to-binder ratio=0.56, FGGM can provide desirable fluidity and 28 d compressive strength, complying with all the requirements for grouting materials. Moreover, the relative error between actual value and predicted value was within a reasonable range, which verifies that RSM can effectively optimize the mix design of FGGM and has accurate prediction ability.