The solid acid in metal-acid bifunctional catalysts for Fischer-Tropsch (FT) synthesis plays a crucial role for one-step selective synthesis of liquid fuels such as gasoline or diesel. In this work, the amorphous silica-alumina (ASA) synthesized by a one-step flame spray pyrolysis method (FSP) was demonstrated for the first time as an efficient solid acid for regulating the product distribution of FT synthesis. The 3 wt.% Ru impregnated ASA with different Al/(Al + Si) ratios was comparatively investigated for FT synthesis under typical conditions. The materials were characterized by XRD, STEM, H-2-TPR, NH3-TPD, and N-2 adsorption/desorption at low temperatures. In comparison with the ASA synthesized by the traditional sol-gel method, the ASA prepared by the FSP method showed clearly increased acidity. As a result, the selectivity of C-13(+) hydrocarbons was decreased while the selectivity of C5-12 hydrocarbons was increased, the extent of which is clearly dependent on the Al/(Al + Si) ratio of ASA. Moreover, both the carbon-chain length and the composition of olefins, normal and branched alkanes of FT products were easily regulated in a certain extent by simply changing the Al/(Al + Si) ratio of ASA. Thus, the enhanced and easily regulated acidity, rich porous structure, and available large-scale production of the ASA originated from FSP method make it an important solid acid for selective synthesis of liquid fuels via FT route.