A novel method was developed to monitor the reaction process and evaluate the sulfonation level in the sulfonation of phthalic anhydride by reversed-phase high-performance liquid chromatography (RP-HPLC). The product peak was identified in chromatograms through product analysis and by comparing its retention time with that of standard compounds. By comparing the hydrolysis and alcoholysis methods, optimized pretreatment of the sample was found for RP-HPLC. Based on the determined percentages of phthalic anhydride and sulfonated phthalic anhydride in the mixture, the degree of sulfonation was calculated. When the sulfonation degree of phthalic anhydride was in the range of 2.8-71%, the recovery of 97-104% was achieved, and the procedure was rapid and accurate.