The uniform design method was used to study the synthesis of high purity mono-alkyl phosphate (MAP) by cyclic polyphosphoric acid. The main factors influencing the content of mono-alkyl phosphate were investigated. The experimental results were analyzed by regression, and the optimum conditions were found to be as follows: mass pentoxide/mass 85 wt% phosphoric acid/mass octanol = 14.2/5.62/48.5, reaction temperature: 115°C, reaction time: 8 h. Under the optimized conditions, a high purity mono-alkyl phosphate with 98.6 wt% MAP yield was obtained.