Novel Fe-Al-SiO2 (FAS) poly-coagulants were prepared by the ball milling method using ferrous sulfate, aluminum sulfate, hydrophobic silica, and sodium carbonate as raw materials. The optimal preparation conditions and effects of preparation parameters on removal efficiencies were obtained by Response Surface Methodology (RSM) and Analysis of Variance (ANOVA). Removal efficiencies were investigated by employing FAS as the poly-coagulant for algae-laden water. Furthermore, obtained FAS samples were characterized by SEM, FTIR, XRD, and TGA. Results showed that the optimal preparation conditions were n(Fe):n(Al) of 2:1, m(Si):m(Fe+Al) of 1:2, and n(CO32−):n(Fe+Al) of 1.75:1, and the most significant influencing factor was n(CO32−):n(Fe+Al). FAS13 prepared under the above condition had the highest coagulation efficiency for simulated algae-laden water. Removal efficiencies for OD680, TP, and residual Al and Fe concentrations were 92.86%, 90.55%, 0.142 mg/L, and 0.074 mg/L, respectively. Nano-sized spherical particles, excellent thermal stability, and functional groups such as Al–O–Si, Fe–O–Si, and Fe–OH, corresponding to Al2Si2O5(OH)4, Fe7Si8O22(OH)2, and Fe2(OH)2CO3, were observed in FAS13. The coagulation performance of FAS13 was splendid when applied in real algae-laden water. The removal rates of TP, OD680, turbidity, and Chl-α were above 93.87%. The residual Al concentration was at the range of 0.057–0.128 mg/L.