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Influenced by geological environment, both fluoride ion and iron ion exceed the standard in underground drinking water sources in some areas. Aiming at this problem, the experiment was designed by Response Surface Methodologyology(RSM). With the goal that fluoride ion in the effluent meets the Standards for Drinking Water quality (GB 5749-2006) and the concentration of iron ion in the effluent drops significantly, the adsorption time, pH value and temperature were taken as independent variables, and the primary and secondary relationship of influencing factors on fluoride and iron reduction of manganese-loaded activated alumina was explored, then the process parameters were optimized. The remarkable relationships are AF(adsorption time)>BF(pH value)>CF(temperature), BFe(pH value) > CFe(temperature)>AFe(adsorption time).Under the conditions of adsorption time 8h, pH value 4 and temperature 25°C, when the mass concentrations of iron and fluorine in raw water are 2mg/L, the removal rates of fluoride and iron can reach 68% and 59.5%, and the mass concentrations of effluent are 0.61mg/L and 0.81mg/L, respectively.